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Kusunoki Y, Fukuoka T, Sugimoto A, Tsujio G, Yonemitsu K, Seki Y, Kasashima H, Shibutani M, Maeda K. Impact of Changes in Psoas Muscle Index on Prognosis in Patients With Colorectal Liver Metastases. CANCER DIAGNOSIS & PROGNOSIS 2025; 5:72-82. [PMID: 39758237 PMCID: PMC11696330 DOI: 10.21873/cdp.10414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 12/02/2024] [Accepted: 12/03/2024] [Indexed: 01/07/2025]
Abstract
Background/Aim Reduction in skeletal muscle mass during chemotherapy is associated with poor outcomes. This study investigated the impact of changes in the psoas muscle index (PMI) on the prognosis of patients with unresectable colorectal liver metastases (CRLM) undergoing chemotherapy, including subgroup analyses based on the initial treatment response assessment. Patients and Methods We evaluated 47 patients with unresectable CRLM who underwent systematic chemotherapy and assessed changes in PMI to determine their prognosis. Results Changes in PMI were significantly associated with the presence or absence of primary tumor resection and the chemotherapeutic responses to first-line chemotherapy. The PMI reduction group was significantly associated with poor prognosis in both overall survival (OS) and progression-free survival (PFS) in patients with CRLM, and in both OS and PFS in the partial response (PR) group at the initial chemotherapy response assessment. Conclusion Skeletal muscle loss at chemotherapy initiation was significantly associated with poorer survival in patients with unresectable CRLM. Maintaining muscle mass could serve as a new indicator for identifying patients with a PR at the initial chemotherapy response assessment for prognosis. Personalized interventions should be investigated to determine whether they can improve muscle mass and lead to better clinical outcomes.
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Affiliation(s)
- Yukina Kusunoki
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Tatsunari Fukuoka
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Atsushi Sugimoto
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Gen Tsujio
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Ken Yonemitsu
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Yuki Seki
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Hiroaki Kasashima
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Masatsune Shibutani
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Kiyoshi Maeda
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
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Depauw L, Townsend A, Karapetis C, Roy A, Wigg A, Tebbutt NC, Chen J, Brooke-Smith M, Price T. Role of locoregional therapy including liver transplantation in liver-only metastatic colorectal cancer: a review paper. Expert Rev Anticancer Ther 2025; 25:41-53. [PMID: 39718339 DOI: 10.1080/14737140.2024.2447360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 12/21/2024] [Accepted: 12/23/2024] [Indexed: 12/25/2024]
Abstract
INTRODUCTION Resection of primary tumor and liver metastases is the gold standard for colorectal cancer with liver-only metastases (CRLM). Although treatment options have expanded to enable conversion of unresectable to resectable CRLM, about 40% of patients will have definitively unresectable disease. Major advances in surgical techniques, immunosuppressive protocols and patient selection criteria for liver transplantation have resulted in improved outcomes. AREAS COVERED A literature search has been conducted in Pubmed for articles published between 2014 and 2024. This review paper comments on current liver-directed treatment options for CRLM: resection, percutaneous ablation, conversion-chemotherapy, TACE, SIRT, and SABR. We explore evidence for liver transplantation in patients with unresectable CRLM, comment on possible limitations for implementation in clinical practice and give an overview of the current guidelines on liver transplantation in the USA, Europe, the United Kingdom, and Australia/New Zealand. EXPERT OPINION The recent randomized TRANSMET trial, investigating liver transplantation versus chemotherapy in unresectable CRLM, shows promising 5-year OS reaching similar values as for other accepted liver transplantation indications. Further investigations with RCTs to investigate reproducibility and feasibility in clinical practice are needed. Before liver transplantation can be implemented as a standard treatment option, reorganizations at federal, regional and hospital levels would be required.
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Affiliation(s)
- Laura Depauw
- Department of Medical Oncology, The Queen Elizabeth Hospital, Woodville, SA, Australia
| | - Amanda Townsend
- Department of Medical Oncology, The Queen Elizabeth Hospital, Woodville, SA, Australia
| | - Christos Karapetis
- College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia
- Department of Medical Oncology, Flinders Medical Centre, Bedford Park, SA, Australia
| | - Amitesh Roy
- College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia
- Department of Medical Oncology, Flinders Medical Centre, Bedford Park, SA, Australia
| | - Alan Wigg
- College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia
- South Australian Liver Transplant Unit, Flinders Medical Centre, Bedford Park, SA, Australia
| | - Niall C Tebbutt
- Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, VIC, Australia
- Department of Surgery, University of Melbourne, Parkville, VIC, Australia
| | - John Chen
- College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia
| | - Mark Brooke-Smith
- College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia
| | - Timothy Price
- Department of Medical Oncology, The Queen Elizabeth Hospital, Woodville, SA, Australia
- Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
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Tang M, Song J, Zhang S, Shu X, Liu S, Ashrafizadeh M, Ertas YN, Zhou Y, Lei M. Innovative theranostic hydrogels for targeted gastrointestinal cancer treatment. J Transl Med 2024; 22:970. [PMID: 39465365 PMCID: PMC11514878 DOI: 10.1186/s12967-024-05749-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 10/08/2024] [Indexed: 10/29/2024] Open
Abstract
Gastrointestinal tumors are the main causes of death among the patients. These tumors are mainly diagnosed in the advanced stages and their response to therapy is unfavorable. In spite of the development of conventional therapeutics including surgery, chemotherapy, radiotherapy and immunotherapy, the treatment of these tumors is still challenging. As a result, the new therapeutics based on (nano)biotechnology have been introduced. Hydrogels are polymeric 3D networks capable of absorbing water to swell with favorable biocompatibility. In spite of application of hydrogels in the treatment of different human diseases, their wide application in cancer therapy has been improved because of their potential in drug and gene delivery, boosting chemotherapy and immunotherapy as well as development of vaccines. The current review focuses on the role of hydrogels in the treatment of gastrointestinal tumors. Hydrogels provide delivery of drugs (both natural or synthetic compounds and their co-delivery) along with gene delivery. Along with delivery, hydrogels stimulate phototherapy (photothermal and photodynamic therapy) in the suppression of these tumors. Besides, the ability of hydrogels for the induction of immune-related cells such as dendritic cells can boost cancer immunotherapy. For more specific cancer therapy, the stimuli-responsive types of hydrogels including thermo- and pH-sensitive hydrogels along with their self-healing ability have improved the site specific drug delivery. Moreover, hydrogels are promising for diagnosis, circulating tumor cell isolation and detection of biomarkers in the gastrointestinal tumors, highlighting their importance in clinic. Hence, hydrogels are diagnostic and therapeutic tools for the gastrointestimal tumors.
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Affiliation(s)
- Min Tang
- Department of Oncology, Chongqing General Hospital, Chongqing University, No.104 Pipa Mountain Main Street, Chongqing, 401120, China
| | - Junzhou Song
- Department of Oncology, BoAo Evergrande International Hospital, Qionghai, 571400, Hainan Province, China
| | - Shuyi Zhang
- Department of Health Management Center, Chongqing General Hospital, Chongqing University, Chongqing, 401120, China
| | - Xiaolei Shu
- Radiation Oncology Center, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Shuang Liu
- Department of Ultrasound, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, No. 120, Longshan Road, Yubei, Chongqing, 401147, China
| | - Milad Ashrafizadeh
- Department of Radiation Oncology, Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, 250000, Shandong, China.
| | - Yavuz Nuri Ertas
- Department of Biomedical Engineering, Erciyes University, 38039, Kayseri, Türkiye
- Department of Technical Sciences, Western Caspian University, AZ1001, Baku, Azerbaijan
| | - Ya Zhou
- Department of Oncology, Chongqing General Hospital, Chongqing University, No.104 Pipa Mountain Main Street, Chongqing, 401120, China.
| | - Ming Lei
- Department of Nuclear Medicine, Chongqing University FuLing Hospital, Chongqing University, No. 2 Gaosuntang Road, Chongqing, China.
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Wiedeman C, Lorraine P, Wang G, Do R, Simpson A, Peoples J, De Man B. Simulated deep CT characterization of liver metastases with high-resolution filtered back projection reconstruction. Vis Comput Ind Biomed Art 2024; 7:13. [PMID: 38861067 PMCID: PMC11166620 DOI: 10.1186/s42492-024-00161-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Accepted: 04/14/2024] [Indexed: 06/12/2024] Open
Abstract
Early diagnosis and accurate prognosis of colorectal cancer is critical for determining optimal treatment plans and maximizing patient outcomes, especially as the disease progresses into liver metastases. Computed tomography (CT) is a frontline tool for this task; however, the preservation of predictive radiomic features is highly dependent on the scanning protocol and reconstruction algorithm. We hypothesized that image reconstruction with a high-frequency kernel could result in a better characterization of liver metastases features via deep neural networks. This kernel produces images that appear noisier but preserve more sinogram information. A simulation pipeline was developed to study the effects of imaging parameters on the ability to characterize the features of liver metastases. This pipeline utilizes a fractal approach to generate a diverse population of shapes representing virtual metastases, and then it superimposes them on a realistic CT liver region to perform a virtual CT scan using CatSim. Datasets of 10,000 liver metastases were generated, scanned, and reconstructed using either standard or high-frequency kernels. These data were used to train and validate deep neural networks to recover crafted metastases characteristics, such as internal heterogeneity, edge sharpness, and edge fractal dimension. In the absence of noise, models scored, on average, 12.2% ( α = 0.012 ) and 7.5% ( α = 0.049 ) lower squared error for characterizing edge sharpness and fractal dimension, respectively, when using high-frequency reconstructions compared to standard. However, the differences in performance were statistically insignificant when a typical level of CT noise was simulated in the clinical scan. Our results suggest that high-frequency reconstruction kernels can better preserve information for downstream artificial intelligence-based radiomic characterization, provided that noise is limited. Future work should investigate the information-preserving kernels in datasets with clinical labels.
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Affiliation(s)
- Christopher Wiedeman
- Department of Electrical and Computer Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA
| | | | - Ge Wang
- Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA
| | - Richard Do
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Amber Simpson
- Biomedical Computing and Informatics, Queen's University, Kingston, ON, K7L 3N6, Canada
| | - Jacob Peoples
- Biomedical Computing and Informatics, Queen's University, Kingston, ON, K7L 3N6, Canada
| | - Bruno De Man
- GE Research - Healthcare, Niskayuna, NY, 12309, USA.
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Kuiper BI, Abu Hilal M, Aldrighetti LA, Björnsson B, D'Hondt M, Dopazo C, Fretland ÅA, Isoniemi H, Philip Jonas J, Kazemier G, Lesurtel M, Primrose J, Schnitzbauer AA, Buffart T, Gruenberger B, Swijnenburg RJ, Gruenberger T. Pan-European survey on current treatment strategies in patients with upfront resectable colorectal liver metastases. HPB (Oxford) 2024; 26:639-647. [PMID: 38373870 DOI: 10.1016/j.hpb.2024.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 11/09/2023] [Accepted: 01/15/2024] [Indexed: 02/21/2024]
Abstract
BACKGROUND There is a lack of consensus on the definition of upfront resectability and use of perioperative systemic therapy for colorectal liver metastases (CRLM). This survey aimed to summarize the current treatment strategies for upfront resectable CRLM throughout Europe. METHODS A survey was sent to all members of the European-African Hepato-Pancreato-Biliary Association to gain insight into the current views on resectability and the use of systemic therapy for upfront resectable CRLM. RESULTS The survey was completed by 87 surgeons from 24 countries. The resectability of CRLM is mostly based on the volume of the future liver remnant, while considering tumor biology. Thermal ablation was considered as an acceptable adjunct to resection in parenchymal-sparing CRLM surgery by 77 % of the respondents. A total of 40.2 % of the respondents preferred standard perioperative systemic therapy and 24.1 % preferred standard upfront local treatment. CONCLUSION Among the participating European hepato-pancreato-biliary surgeons, there is a high degree of consensus on the definition of CRLM resectability. However, there is much variety in the use of adjunctive thermal ablation. Major variations persist in the use of perioperative systemic therapy in cases of upfront resectable CRLM, stressing the need for further evidence and a consensus.
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Affiliation(s)
- Babette I Kuiper
- Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, De Boelelaan 1117, Amsterdam, the Netherlands; Cancer Center Amsterdam, Treatment and Quality of Life, Amsterdam, the Netherlands
| | - Mohammad Abu Hilal
- Department of Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | - Luca A Aldrighetti
- Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Milan, Italy
| | - Bergthor Björnsson
- Department of Biomedical and Clinical Sciences, Division of Surgery, Linköping University, Linköping, Sweden
| | - Mathieu D'Hondt
- Department of Digestive and Hepatobiliary/Pancreatic Surgery, Groeninge Hospital, Kortrijk, Belgium
| | - Cristina Dopazo
- Department of HPB Surgery and Transplants, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Åsmund A Fretland
- The Intervention Centre and Department of HPB Surgery, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Helena Isoniemi
- Department of Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - J Philip Jonas
- Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Geert Kazemier
- Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, De Boelelaan 1117, Amsterdam, the Netherlands; Cancer Center Amsterdam, Treatment and Quality of Life, Amsterdam, the Netherlands
| | - Mickael Lesurtel
- Department of HPB Surgery and Liver Transplantation, DMU DIGEST, AP-HP, Hôpital Beaujon, Clichy, France
| | - John Primrose
- University Department of Surgery, University Hospital Southampton, Southampton, United Kingdom
| | | | - Tineke Buffart
- Cancer Center Amsterdam, Treatment and Quality of Life, Amsterdam, the Netherlands; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Medical Oncology, De Boelelaan 1117, Amsterdam, the Netherlands
| | - Birgit Gruenberger
- Department of Oncology & Haematology, Wr Neustadt Hospital, Wr Neustadt, Austria
| | - Rutger-Jan Swijnenburg
- Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, De Boelelaan 1117, Amsterdam, the Netherlands; Cancer Center Amsterdam, Treatment and Quality of Life, Amsterdam, the Netherlands.
| | - Thomas Gruenberger
- Department of Surgery, HPB Center Vienna Health Network, Clinic Favoriten and Sigmund Freud Private University, Vienna, Austria
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Dumarco RB, Fonseca GM, Coelho FF, Jeismann VB, Makdissi FF, Kruger JAP, Nahas SC, Herman P. Multiple colorectal liver metastases resection can offer long-term survival: The concept of a chronic neoplastic disease. Surgery 2023; 173:983-990. [PMID: 36220666 DOI: 10.1016/j.surg.2022.08.032] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 08/25/2022] [Accepted: 08/27/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND Resection for colorectal liver metastases has evolved significantly and, currently, there are no limits to the number of resected nodules. This study aimed to evaluate the outcomes and prognostic factors after liver resection for patients with ≥4 colorectal liver metastases, emphasizing long-term survival. METHODS The study population consisted of 137 patients with ≥4 colorectal liver metastases out of a total of 597 patients with colorectal liver metastases who underwent curative intent liver resection from January 2010 to July 2019 in a single hepatobiliary center. RESULTS The probability of overall and disease-free survival at 1, 3, and 5 years was 90.8%, 64.5%, 40.6%, and 37.7%, 19.3%, 18.1%, respectively. In a multivariate analysis for overall survival, the size of the largest metastatic nodule was the only unfavorable factor (P = .001). For disease-free survival, complete pathological response was a favorable factor (P = .04), and the following were negative factors: number of nodules ≥7 (P = .034), radiofrequency ablation during surgery (P = .04), positive primary tumor lymph nodes (P = .034), R1 resection (P = .011), and preoperative carcinoembryonic antigen >20 ng/mL (P = .015). After the first and second years of follow-up, 59 patients (45.3%) and 45 patients (34.6%), respectively, were not receiving chemotherapy. After 5 years of follow-up, 21 (16.1%) multimetastatic patients were chemotherapy-free. CONCLUSION A significant number of patients with multiple colorectal liver metastases will present long-term survival and should not be denied surgery. The long-term survival rates, even in the presence of recurrence, characterize a chronic neoplastic disease.
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Affiliation(s)
- Rodrigo Blanco Dumarco
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil
| | - Gilton Marques Fonseca
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil. https://twitter.com/medgilton
| | - Fabricio Ferreira Coelho
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil
| | - Vagner Birk Jeismann
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil. https://twitter.com/vjeismann
| | - Fabio Ferrari Makdissi
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil
| | - Jaime Arthur Pirolla Kruger
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil
| | - Sergio Carlos Nahas
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil. https://twitter.com/SergioNahasDr
| | - Paulo Herman
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil.
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Tammaro V, Carlomagno N, Santangelo M, Calogero A, Dodaro CA, Vernillo A, Sica A, Peluso G, Campanile S, Sagnelli E, Sagnelli C. One-stage resection of primary colorectal cancer and hepatic metastases using the Habib Device: analysis of 40 consecutive cases treated in a Unit of general surgery. Minerva Med 2022; 113:846-852. [PMID: 32407049 DOI: 10.23736/s0026-4806.20.06613-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND More than 50% of patients with colorectal cancer (CRC) present or develop hepatic metastases (HM). The intraoperative use of the Habib 4X® radio frequency probe device is safe in resetting HM and allows a one-stage resection of both CRC and HM with a similar mortality rate than a two-stage surgical treatment. METHODS After an exhaustive residential training at the reference center for hepato-biliary surgery of the Imperial College of London, we treated at our unit of general surgery 40 consecutive patients with CRC and HM with the one-stage resection, using the Habib 4X® intraoperative radiofrequency probe device to reset HM. RESULTS None of the 40 patients died during the intra-operatory and post-operatory periods, none presented liver failures during the postoperative course nor complication related to the Habib's resection procedure (e.g. bleeding, abscess, bile leak). The amount of intra-operative liver bleeding was minimal. New HM arose in 10 (25%) cases, with a mean disease-free interval of 13 months, but the hepatic tissue close to previous resections remained cancer-free. The 69.7% of patients were disease-free at month 24 of the post-operative follow-up and 5-year rate was about 70%. CONCLUSIONS The data suggest that surgeons well trained at a reference center for hepato-biliary surgery may perform with excellent results the one-stage CRC and HM resection with the Habib 4X® device even in a Unit of general surgery.
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Affiliation(s)
- Vincenzo Tammaro
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy -
| | - Nicola Carlomagno
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Michele Santangelo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Armando Calogero
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Concetta A Dodaro
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Antonio Vernillo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Antonello Sica
- Department of Precision Medicine, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Gaia Peluso
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Silvia Campanile
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Luigi Vanvitelli University of Campania, Naples, Italy
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Outcomes of simultaneous laparoscopic, hybrid, and open resection in colorectal cancer with synchronous liver metastases: a propensity score-matched study. Sci Rep 2022; 12:8867. [PMID: 35614070 PMCID: PMC9132984 DOI: 10.1038/s41598-022-12372-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 04/27/2022] [Indexed: 11/08/2022] Open
Abstract
We aimed to compare the short- and long-term outcomes of simultaneous laparoscopic, hybrid, and open resection for colorectal cancer and synchronous liver metastases. We retrospectively analyzed the data of 647 patients with simultaneous resection of colorectal cancer and liver metastases between January 2006 and December 2018 at three tertiary referral hospitals. Patient’s baseline characteristics, perioperative outcomes, pathological examination results, liver-specific recurrence rate and survivals were compared between the propensity score-matched groups. Forty-two and 81 patients were selected for the laparoscopic vs. hybrid groups, and 48 and 136 patients for laparoscopic vs. open groups, respectively. The laparoscopic group had fewer wound complications (2.1 vs. 13.2%; p = 0.028) than the open group, and a shorter postoperative hospital stay than the hybrid and open groups (8 vs. 11 days, p < 0.001 for both). The 5-year liver-specific recurrence rates were 38.7% and 46.0% in the laparoscopic and hybrid groups, respectively (p = 0.270), and 34.0% and 37.0% in the laparoscopic and open groups, respectively (p = 0.391). Simultaneous laparoscopic resection for colorectal cancer and liver metastases can be performed safely with significantly enhanced postoperative recovery and comparable long-term outcomes compared to hybrid and open resection.
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9
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Shapera E, Ross SB, Chudzinski A, Massarotti H, Syblis CC, Crespo K, Rosemurgy AS, Sucandy I. Simultaneous Resection of Colorectal Carcinoma and Hepatic Metastases is Safe and Effective: Examining the Role of the Robotic Approach. Am Surg 2022:31348221093533. [PMID: 35487498 DOI: 10.1177/00031348221093533] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUNDS AND OBJECTIVES Up to 50% of patients with colorectal carcinoma (CRC) present with liver metastases (CLM) throughout their course. Complete resection of both sites provides the only chance for cure. Either a staged or simultaneous resection is feasible. The latter avoids delays in adjuvant systemic chemotherapy but may increase technical complexity and perioperative complications. We aim to evaluate our initial outcomes of simultaneous CRC and CLM resections with a focus on the robotic technique. METHOD With institutional review board approval, we followed 26 consecutive patients who underwent simultaneous/concomitant liver and colorectal resection. Major liver resection is defined as resection of ≥3 contiguous Couinaud segments. Data are presented as median (mean ± SD). RESULTS Patients were 64 (63 ± 14.0) years old. Body mass index was 29 (29 ± 5.7) kg/m2. 54% of patients had prior abdominal operation(s). A majority of patients were >ASA class III (73%), underwent major liver resection (62%) with robotic approach (77%). In the robotic cohort, there were no unplanned conversions to open. Estimated blood loss was 150 (210 ± 181.8) ml. Total operative duration was 446 (463 ± 93.6) minutes. Negative margins (R0) were obtained in all patients. Postoperative complication of Clavien-Dindo≥3 occurred in three patients, including one requiring reoperation with end ileostomy for anastomotic leak. Length of stay was 5 (6 ± 3.5) days. Three patients were readmitted within 30 days after discharge, none for reoperation. There was no 90-day mortality. CONCLUSION Our cohort of concomitant CRC and CLM resection demonstrates safety and efficacy via both the open and robotic approach.
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Affiliation(s)
| | - Sharona B Ross
- Digestive Health Institute, 4422AdventHealth Tampa, Tampa, FL, USA
| | - Allen Chudzinski
- Digestive Health Institute, 4422AdventHealth Tampa, Tampa, FL, USA
| | - Haane Massarotti
- Digestive Health Institute, 4422AdventHealth Tampa, Tampa, FL, USA
| | - Cameron C Syblis
- Digestive Health Institute, 4422AdventHealth Tampa, Tampa, FL, USA
| | - Kaitlyn Crespo
- Digestive Health Institute, 4422AdventHealth Tampa, Tampa, FL, USA
| | | | - Iswanto Sucandy
- Digestive Health Institute, 4422AdventHealth Tampa, Tampa, FL, USA
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10
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Hernandez-Alejandro R, Ruffolo LI, Sasaki K, Tomiyama K, Orloff MS, Pineda-Solis K, Nair A, Errigo J, Dokus MK, Cattral M, McGilvray ID, Ghanekar A, Gallinger S, Selzner N, Claasen MPAW, Burkes R, Hashimoto K, Fujiki M, Quintini C, Estfan BN, Kwon CHD, Menon KVN, Aucejo F, Sapisochin G. Recipient and Donor Outcomes After Living-Donor Liver Transplant for Unresectable Colorectal Liver Metastases. JAMA Surg 2022; 157:524-530. [PMID: 35353121 PMCID: PMC8968681 DOI: 10.1001/jamasurg.2022.0300] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Question What are the estimated overall and recurrence-free survival outcomes after living-donor liver transplant (LDLT) in patients with liver-confined, unresectable colorectal cancer liver metastasis (CRLM)? Findings In this cohort study of 10 adults with CRLM who received LDLT, Kaplan-Meier estimates of recurrence-free and overall survival at a median follow-up of 1.5 years were 62% and 100%, respectively. Perioperative outcomes for both recipients and donors were consistent with established benchmarks. Meaning The results suggest that LDLT may be a viable treatment option for select patients with unresectable CRLMs with favorable tumor biology. Importance Colorectal cancer is a leading cause of cancer-related death, and nearly 70% of patients with this cancer have unresectable colorectal cancer liver metastases (CRLMs). Compared with chemotherapy, liver transplant has been reported to improve survival in patients with CRLMs, but in North America, liver allograft shortages make the use of deceased-donor allografts for this indication problematic. Objective To examine survival outcomes of living-donor liver transplant (LDLT) for unresectable, liver-confined CRLMs. Design, Setting, and Participants This prospective cohort study included patients at 3 North American liver transplant centers with established LDLT programs, 2 in the US and 1 in Canada. Patients with liver-confined, unresectable CRLMs who had demonstrated sustained disease control on oncologic therapy met the inclusion criteria for LDLT. Patients included in this study underwent an LDLT between July 2017 and October 2020 and were followed up until May 1, 2021. Exposures Living-donor liver transplant. Main Outcomes and Measures Perioperative morbidity and mortality of treated patients and donors, assessed by univariate statistics, and 1.5-year Kaplan-Meier estimates of recurrence-free and overall survival for transplant recipients. Results Of 91 evaluated patients, 10 (11%) underwent LDLT (6 [60%] male; median age, 45 years [range, 35-58 years]). Among the 10 living donors, 7 (70%) were male, and the median age was 40.5 years (range, 27-50 years). Kaplan-Meier estimates for recurrence-free and overall survival at 1.5 years after LDLT were 62% and 100%, respectively. Perioperative morbidity for both donors and recipients was consistent with established standards (Clavien-Dindo complications among recipients: 3 [10%] had none, 3 [30%] had grade II, and 4 [40%] had grade III; donors: 5 [50%] had none, 4 [40%] had grade I, and 1 had grade III). Conclusions and Relevance This study’s findings of recurrence-free and overall survival rates suggest that select patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT.
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Affiliation(s)
- Roberto Hernandez-Alejandro
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Luis I Ruffolo
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Kazunari Sasaki
- Department of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Koji Tomiyama
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Mark S Orloff
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Karen Pineda-Solis
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Amit Nair
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Jennie Errigo
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - M Katherine Dokus
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Mark Cattral
- HPB and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, Toronto, Ontario, Canada
| | - Ian D McGilvray
- HPB and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, Toronto, Ontario, Canada
| | - Anand Ghanekar
- HPB and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, Toronto, Ontario, Canada
| | - Steven Gallinger
- HPB and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, Toronto, Ontario, Canada
| | - Nazia Selzner
- HPB and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, Toronto, Ontario, Canada
| | - Marco P A W Claasen
- HPB and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, Toronto, Ontario, Canada.,Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | - Ron Burkes
- HPB and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, Toronto, Ontario, Canada
| | - Koji Hashimoto
- Department of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Masato Fujiki
- Department of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Cristiano Quintini
- Department of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Bassam N Estfan
- Department of Gastrointestinal Oncology, Cancer Institute, Cleveland Clinic, Cleveland, Ohio
| | | | - K V Narayanan Menon
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Federico Aucejo
- Department of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Gonzalo Sapisochin
- HPB and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, Toronto, Ontario, Canada
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11
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Analysis of surgical approach and tumor distance to margin after liver resection for colorectal liver metastasis. J Robot Surg 2022; 16:1427-1439. [PMID: 35199291 DOI: 10.1007/s11701-022-01387-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 02/06/2022] [Indexed: 02/07/2023]
Abstract
This study was undertaken to compare tumor distance to margin after robotic vs. open hepatectomy for colorectal liver metastases (CLM) and to determine the relationship between perioperative variables, surgical approach and tumor distance to margin with overall survival. With IRB approval, we followed 56 patients who underwent a robotic or open hepatectomy for treatment of CLM. The relationships between the tumor distance to margin, operative approach, perioperative variables and survival was determined. The robotic approach yielded greater margins than the open approach (p = 0.04). The robotic vs. open approach had an operative duration of 375 vs. 269 min (p = 0.05), ICU length of stay (LOS) of 0 vs. 1 day (p = 0.01), and hospital LOS of 4 vs. 7 days (p = 0.04). Patients with a tumor distance to margin of ≤ 1 mm and 1.1-9.9 mm had an estimated median survival of 49 months and 24 months, respectively. Estimated median survival for patients with tumor distance to margin of ≥ 10 mm has not been reached but is > 84 months. The use of the robotic approach is associated with greater tumor distance to margin and shorter hospital LOS, but with longer operations. The robotic approach does not compromise oncological margins during resection for CLM.
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12
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Kanikarla Marie P, Fowlkes NW, Afshar-Kharghan V, Martch SL, Sorokin A, Shen JP, Morris VK, Dasari A, You N, Sood AK, Overman MJ, Kopetz S, Menter DG. The Provocative Roles of Platelets in Liver Disease and Cancer. Front Oncol 2021; 11:643815. [PMID: 34367949 PMCID: PMC8335590 DOI: 10.3389/fonc.2021.643815] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 06/30/2021] [Indexed: 12/12/2022] Open
Abstract
Both platelets and the liver play important roles in the processes of coagulation and innate immunity. Platelet responses at the site of an injury are rapid; their immediate activation and structural changes minimize the loss of blood. The majority of coagulation proteins are produced by the liver—a multifunctional organ that also plays a critical role in many processes: removal of toxins and metabolism of fats, proteins, carbohydrates, and drugs. Chronic inflammation, trauma, or other causes of irreversible damage to the liver can dysregulate these pathways leading to organ and systemic abnormalities. In some cases, platelet-to-lymphocyte ratios can also be a predictor of disease outcome. An example is cirrhosis, which increases the risk of bleeding and prothrombotic events followed by activation of platelets. Along with a triggered coagulation cascade, the platelets increase the risk of pro-thrombotic events and contribute to cancer progression and metastasis. This progression and the resulting tissue destruction is physiologically comparable to a persistent, chronic wound. Various cancers, including colorectal cancer, have been associated with increased thrombocytosis, platelet activation, platelet-storage granule release, and thrombosis; anti-platelet agents can reduce cancer risk and progression. However, in cancer patients with pre-existing liver disease who are undergoing chemotherapy, the risk of thrombotic events becomes challenging to manage due to their inherent risk for bleeding. Chemotherapy, also known to induce damage to the liver, further increases the frequency of thrombotic events. Depending on individual patient risks, these factors acting together can disrupt the fragile balance between pro- and anti-coagulant processes, heightening liver thrombogenesis, and possibly providing a niche for circulating tumor cells to adhere to—thus promoting both liver metastasis and cancer-cell survival following treatment (that is, with minimal residual disease in the liver).
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Affiliation(s)
- Preeti Kanikarla Marie
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Natalie W Fowlkes
- Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Vahid Afshar-Kharghan
- Division of Internal Medicine, Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Stephanie L Martch
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Alexey Sorokin
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - John Paul Shen
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Van K Morris
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Arvind Dasari
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Nancy You
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Anil K Sood
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Michael J Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - David George Menter
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Alam W, Bouferraa Y, Haibe Y, Mukherji D, Shamseddine A. Management of colorectal cancer in the era of COVID-19: Challenges and suggestions. Sci Prog 2021; 104:368504211010626. [PMID: 33878982 PMCID: PMC10358474 DOI: 10.1177/00368504211010626] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The Coronavirus (COVID-19) pandemic had a huge impact on all sectors around the world. In particular, the healthcare system has been subject to an enormous pressure that has surpassed its ability in many instances. Additionally, the pandemic has called for a review of our daily medical practices, including our approach to colorectal cancer management where treatment puts patients at high risk of virus exposure. Given their higher median age, patients are at an increased risk for severe symptoms and complications in cases of infection, especially in the setting of immunosuppression. Therefore, a review of the routine colorectal cancer practices is needed to minimize risk of exposure. Oncologists should weigh risk of exposure versus the patient's oncologic benefits when approaching management. In addition, treatment protocols should be modified to minimize hospital visits and admissions while maintaining the same treatment efficacy. In this review, we will focus on challenges that colorectal cancer patients face during the pandemic, while highlighting the priority in each case. We will also discuss the evidence for potential modifications to existing treatment plans that could reduce infectious exposure without compromising care. Finally, we will discuss the impact of the socio-economic difficulties faced by Lebanese patients due to a poor economy toppled by an unexpected pandemic.
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Affiliation(s)
- Walid Alam
- Department of Internal Medicine, Division of Hematology-Oncology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Youssef Bouferraa
- Department of Internal Medicine, Division of Hematology-Oncology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Yolla Haibe
- Department of Internal Medicine, Division of Hematology-Oncology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Deborah Mukherji
- Department of Internal Medicine, Division of Hematology-Oncology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ali Shamseddine
- Department of Internal Medicine, Division of Hematology-Oncology, American University of Beirut Medical Center, Beirut, Lebanon
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14
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Innovations in liver transplantation in 2020, position of the Belgian Liver Intestine Advisory Committee (BeLIAC). Acta Gastroenterol Belg 2021; 84:347-359. [PMID: 34217187 DOI: 10.51821/84.2.347] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver transplantation (LT) remains the only curative option for patients suffering from end-stage liver disease, acute liver failure and selected hepatocellular carcinomas and access to the LT-waiting list is limited to certain strict indications. However, LT has shown survival advantages for patients in certain indications such as acute alcoholic hepatitis, hepatocellular carcinoma outside Milan criteria and colorectal cancer metastases. These newer indications increase the pressure in an already difficult context of organ shortage. Strategies to increase the transplantable organ pool are therefore needed. We will discuss here the use of HCV positive grafts as the use of normothermic isolated liver perfusion. Belgian Liver Intestine Advisory Committee (BeLIAC) from the Belgian Transplant Society (BTS) aims to guarantee the balance between the new indications and the available resources.
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15
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Yoshikawa M, Morine Y, Yamada S, Miyazaki K, Tokuda K, Saito Y, Arakawa Y, Ikemoto T, Imura S, Shimada M. Prognostic prediction of resectable colorectal liver metastasis using the apparent diffusion coefficient from diffusion-weighted magnetic resonance imaging. Ann Gastroenterol Surg 2021; 5:252-258. [PMID: 33860146 PMCID: PMC8034686 DOI: 10.1002/ags3.12404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 08/01/2020] [Accepted: 09/09/2020] [Indexed: 11/09/2022] Open
Abstract
AIM Diffusion-weighted magnetic resonance imaging (DWI-MRI) is used to predict tumor malignancy. Here we explored the role of apparent diffusion coefficient (ADC) values in the treatment of patients with resectable colorectal liver metastasis (CRLM). METHODS Magnetic resonance imaging (MRI) scans were conducted using a Signa HDe or Signa Explorer 1.5-T scanner (GE Healthcare). ADC maps were calculated using DWI with b values of 0, 20, and 800 s/mm2. We enrolled 60 patients who underwent upfront hepatic resection for CRLM and divided them into ADC-high (n = 30) and ADC-low (n = 30) groups. Clinicopathological variables of the groups were compared. Immunohistochemical analysis of HIF-1α expression in tumor tissues was performed, and the relationship between the ADC value and HIF-1α expression was evaluated. RESULTS The disease-free survival rate of the ADC-low group was significantly lower than that of the ADC-high group (P < .05). Univariate analysis revealed that tumor number (more than five), synchronous metastasis, and low ADC were prognostic factors. Multivariate analysis identified low ADC as an independent prognostic factor. Furthermore, the ADC-low group more frequently expressed high levels of HIF-1α than the ADC-high group. CONCLUSION Low ADC values were an independent prognostic factor of resectable CRLM and correlated with HIF-1α expression.
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Affiliation(s)
- Masato Yoshikawa
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Yuji Morine
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Shinichiro Yamada
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Katsuki Miyazaki
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Kazunori Tokuda
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Yu Saito
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Yusuke Arakawa
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Tetsuya Ikemoto
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Satoru Imura
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Mitsuo Shimada
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
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16
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Kawakatsu S, Ishizawa T, Fujimoto Y, Oba A, Mise Y, Inoue Y, Ito H, Takahashi Y, Ueno M, Saiura A. Impact on operative outcomes of laparoscopic simultaneous resection of colorectal cancer and synchronous liver metastases. Asian J Endosc Surg 2021; 14:34-43. [PMID: 32246587 DOI: 10.1111/ases.12802] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Revised: 02/27/2020] [Accepted: 03/05/2020] [Indexed: 01/20/2023]
Abstract
INTRODUCTION The efficacy of laparoscopic simultaneous resection of primary colorectal cancer and synchronous colorectal liver metastases (SCRLM) remains unclear. METHODS We retrospectively evaluated data from 258 patients who had undergone simultaneous curative resection of the primary tumor and SCRLM from 2006 to 2017. We compared surgical outcomes between open, hybrid (laparoscopic colorectal resection and open hepatectomy), and pure laparoscopic approaches. Surgical outcomes were also evaluated between the open hepatectomy (OH) group (ie, open/hybrid surgery) and the laparoscopic hepatectomy (LH) group (ie, pure laparoscopic surgery) in 141 patients later in the study period (2013-2017), when the clinical indications for laparoscopic hepatectomy were restricted to simple wedge resection and/or left lateral sectionectomy in our center. RESULTS The pure laparoscopic approach was associated with significantly less intraoperative blood loss and a significantly shorter postoperative hospital stay than the open and hybrid approaches. Late in the study period, operative outcomes in the LH group (n = 37) were more favorable than for the OH group (n = 104) in terms of intraoperative blood loss and postoperative hospital stay. In patients with rectal cancer, however, earlier postoperative recovery in the LH group did not differ significantly from the OH group. CONCLUSION Laparoscopic simultaneous resection of SCRLM with the primary tumor by simple hepatectomy is safe and may enhance patients' postoperative recovery, especially in patients with colon cancer.
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Affiliation(s)
- Shoji Kawakatsu
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takeaki Ishizawa
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.,Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Yoshiya Fujimoto
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Atsushi Oba
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yoshihiro Mise
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.,Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yousuke Inoue
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hiromichi Ito
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yu Takahashi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masashi Ueno
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akio Saiura
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.,Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan
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17
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Xiao B, Peng J, Wang Y, Deng Y, Ou Q, Wu X, Lin J, Pan Z, Zhang L. Prognostic value of tumor infiltrating lymphocytes combined with PD-L1 expression for patients with solitary colorectal cancer liver metastasis. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1221. [PMID: 33178753 PMCID: PMC7607072 DOI: 10.21037/atm-20-2762a] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Background The aim of this study was to assess the prognostic value of CD8+ tumor infiltrating lymphocytes (TIL) combined with programmed cell death-ligand 1 (PD-L1) expression for patients with solitary colorectal cancer liver metastasis (SCLM) undergoing R0 resection Methods Patients undergoing curative hepatectomy for SCLM were reviewed. Immunohistochemical multiplex technique was used for quantifying CD8+ TIL, and immunohistochemical staining was used for assessing PD-L1 expression. The tumor immune microenvironment (TIME) was classified as strong for high CD8+ TIL and low PD-L1, weak for low CD8+ TIL and high PD-L1, and mild for the rest. Recurrence-free survival (RFS) and overall survival (OS) was compared between these groups. Results Among the 94 patients included, a high CD8+ TIL and high PD-L1 expression was observed in 51 (54.3%) and 47 (50.0%) patients, respectively. Strong, mild, and weak TIME was observed in 24 (25.5%), 42 (44.7%), and 28 (29.8%) patients, respectively. Patients with a high CD8+ TIL had a significant longer RFS than patients with a low CD8+ TIL (3-year RFS rate, 71.6% vs. 55.3%, P=0.018). The 3-year RFS rate in the strong TIME group was significantly higher than that in the mild and weak TIME groups (89.5% vs. 71.7% and 28.8%, P<0.001), as was the 3-year rate of OS (93.8% vs. 81.8% and 61.6%, P<0.001). CD8+ TIL combined with PD-L1 expression showed better predicting accuracy for RFS than CD8+ TIL alone. Conclusions The density of CD8+ TIL combined with PD-L1 expression in liver metastasis was a predictor of RFS for patients with SCLM undergoing R0 resection, and therefore can be used for guiding the postoperative treatment of these patients.
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Affiliation(s)
- Binyi Xiao
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangzhou, China
| | - Jianhong Peng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangzhou, China
| | - Yongchun Wang
- Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangzhou, China
| | - Yuxiang Deng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangzhou, China
| | - Qingjian Ou
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangzhou, China.,Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangzhou, China
| | - Xiaojun Wu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangzhou, China
| | - Junzhong Lin
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangzhou, China
| | - Zhizhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangzhou, China
| | - Lin Zhang
- Department of Medicine Laboratory, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, China.,Department of Clinical Laboratory, Yunfu People's Hospital, Yunfu, China
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Lee KS, Suchett-Kaye I, Abbadi R, Finch-Jones M, Pope I, Strickland A, Rees J. Microscopic resection margins adversely influence survival rates after surgery for colorectal liver metastases: An open ambidirectional Cohort Study. Int J Surg 2020; 83:8-14. [PMID: 32927149 DOI: 10.1016/j.ijsu.2020.09.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 08/25/2020] [Accepted: 09/03/2020] [Indexed: 01/17/2023]
Abstract
BACKGROUND Liver resection is the most effective treatment for patients with colorectal liver metastases (CRLMs). Patients with tumour at the resection margin (R1) are reported to have worse survival compared to those with an uninvolved resection margin (R0). Recent data has questioned this finding. This study investigates whether R1 resections adversely influence survival when compared to R0 resections. MATERIAL AND METHODS Patients undergoing surgery for CRLM, identified from a prospectively maintained database, from January 2007 to January 2017, were included. Univariate and multivariate survival analyses were performed. p < 0.05 was significant. RESULTS 282 patients were included. Median age 72 (32-90) years. 236 patients (83.7%) had chemotherapy and surgery, whilst 46 (16.3%) had surgery alone. 149 patients (52.8%) were alive at the end of the study period. R1 resection on univariate survival analysis was associated with better survival (HR 2.12, 95%CI 1.60-4.61, p = 0.0002). Multivariate analysis controlling for age and gender, identified presence of extrahepatic disease (HR 2.03, 95%CI 1.17-3.52, p < 0.001), R0 resection (HR 0.33, 95%CI 0.19-0.59, p = 0.003), primary tumour stage (HR 1.57, 95%CI 1.04-2.40, p = 0.034) and primary tumour differentiation (HR 2.56, 95%CI 1.01-6.46, p = 0.047), as prognostic factors for poorer survival. Five-year and 10-year survival were 54.3% and 41.7% respectively in patients with an R0 resection and, 25.8% and 17.2% in those with an R1 resection. CONCLUSION The presence of extrahepatic disease, an R1 resection margin, advanced T-stage and poorer tumour differentiation were associated with worse survival in CRLM surgery and R0 resection is recommended.
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Affiliation(s)
- Keng Siang Lee
- University Hospitals Bristol NHS Foundation Trust, Bristol, BS2 8HW, UK; Bristol Medical School, University of Bristol, Bristol, BS8 1QU, UK; Centre for Surgical Research, University of Bristol, Canynge Hall, 39, Whatley Road, Bristol, BS8 2PS, UK.
| | - Ivo Suchett-Kaye
- Bristol Medical School, University of Bristol, Bristol, BS8 1QU, UK.
| | - Reyad Abbadi
- University Hospitals Bristol NHS Foundation Trust, Bristol, BS2 8HW, UK.
| | - Meg Finch-Jones
- University Hospitals Bristol NHS Foundation Trust, Bristol, BS2 8HW, UK.
| | - Ian Pope
- University Hospitals Bristol NHS Foundation Trust, Bristol, BS2 8HW, UK.
| | - Andrew Strickland
- University Hospitals Bristol NHS Foundation Trust, Bristol, BS2 8HW, UK.
| | - Jonathan Rees
- University Hospitals Bristol NHS Foundation Trust, Bristol, BS2 8HW, UK; Bristol Medical School, University of Bristol, Bristol, BS8 1QU, UK; Centre for Surgical Research, University of Bristol, Canynge Hall, 39, Whatley Road, Bristol, BS8 2PS, UK.
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Hamm A, Hidding S, Mokry T, Radeleff B, Mehrabi A, Büchler MW, Schneider M, Schmidt T. Postoperative liver regeneration does not elicit recurrence of colorectal cancer liver metastases after major hepatectomy. Surg Oncol 2020; 35:24-33. [PMID: 32818879 DOI: 10.1016/j.suronc.2020.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 07/06/2020] [Accepted: 07/21/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND OBJECTIVES Recurrence is a frequent concern in curatively resected CRC liver metastases. Translational research suggests that regeneration upon hepatectomy may also alleviate metastatic recurrence; however, the significance in patients is unclear. We therefore sought to study the effect of liver regeneration on tumor recurrence in patients. METHODS In this retrospective cohort study, we included 58 out of 186 potentially eligible patients from our prospectively maintained database of CRC liver metastasis patients between 2001 and 2012 with a median follow-up of 42 months who underwent a formal right or left hemihepatectomy. Liver regeneration in CT volumetry was correlated with recurrence of CRC liver metastases and overall survival. RESULTS Liver regeneration increased up to 14 months to 21.0% for left and 122.6% for right hemihepatectomy, respectively, with comparable final volumes. Regeneration was independent of initial tumor stage, number of metastases, and preoperative chemotherapy. Patients with lower liver regeneration showed earlier recurrence of CRC liver metastases (p = 0.006). Overall survival did not differ in patients with weak versus strong liver regeneration. CONCLUSIONS The extent of liver regeneration after major hepatectomy does not impede overall survival. Therefore, our data encourage aggressive therapeutical regimes for CRC liver metastases involving major hepatectomies as part of a curative approach.
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Affiliation(s)
- Alexander Hamm
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Sarah Hidding
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Theresa Mokry
- Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Boris Radeleff
- Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Martin Schneider
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Thomas Schmidt
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.
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Wang P, Sun S, Ma H, Sun S, Zhao D, Wang S, Liang X. Treating tumors with minimally invasive therapy: A review. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2019; 108:110198. [PMID: 31923997 DOI: 10.1016/j.msec.2019.110198] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Revised: 09/01/2019] [Accepted: 09/11/2019] [Indexed: 12/13/2022]
Abstract
With high level of morbidity and mortality, tumor is one of the deadliest diseases worldwide. Aiming to tackle tumor, researchers have developed a lot of strategies. Among these strategies, the minimally invasive therapy (MIT) is very promising, for its capability of targeting tumor cells and resulting in a small incision or no incisions. In this review, we will first illustrate some mechanisms and characteristics of tumor metastasis from the primary tumor to the secondary tumor foci. Then, we will briefly introduce the history, characteristics, and advantages of some of the MITs. Finally, emphasis will be, respectively, focused on an overview of the state-of-the-art of the HIFU-, PDT-, PTT-and SDT-based anti-tumor strategies on each stage of tumor metastasis.
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Affiliation(s)
- Ping Wang
- Department of Ultrasound, Peking University Third Hospital, Beijing, 100191, China
| | - Suhui Sun
- Department of Ultrasound, Peking University Third Hospital, Beijing, 100191, China
| | - Huide Ma
- Ordos Center Hospital, Ordos, Inner Mongolia, 017000, China
| | - Sujuan Sun
- Ordos Center Hospital, Ordos, Inner Mongolia, 017000, China
| | - Duo Zhao
- Ordos Center Hospital, Ordos, Inner Mongolia, 017000, China
| | - Shumin Wang
- Department of Ultrasound, Peking University Third Hospital, Beijing, 100191, China.
| | - Xiaolong Liang
- Department of Ultrasound, Peking University Third Hospital, Beijing, 100191, China.
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Symonds LK, Cohen SA. Use of perioperative chemotherapy in colorectal cancer metastatic to the liver. Gastroenterol Rep (Oxf) 2019; 7:301-311. [PMID: 31687149 PMCID: PMC6821343 DOI: 10.1093/gastro/goz035] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 06/06/2019] [Accepted: 07/18/2019] [Indexed: 12/22/2022] Open
Abstract
A curative-intent approach may improve survival in carefully selected patients with oligometastatic colorectal cancer. Aggressive treatments are most frequently administered to patients with isolated liver metastasis, though they may be judiciously considered for other sites of metastasis. To be considered for curative intent with surgery, patients must have disease that can be definitively treated while leaving a sufficient functional liver remnant. Neoadjuvant chemotherapy may be used for upfront resectable disease as a test of tumor biology and/or for upfront unresectable disease to increase the likelihood of resectability (so-called 'conversion' chemotherapy). While conversion chemotherapy in this setting aims to improve survival, the choice of a regimen remains a complex and highly individualized decision. In this review, we discuss the role of RAS status, primary site, sidedness, and other clinical features that affect chemotherapy treatment selection as well as key factors of patients that guide individualized patient-treatment recommendations for colorectal-cancer patients being considered for definitive treatment with metastasectomy.
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Affiliation(s)
- Lynn K Symonds
- Division of Oncology, University of Washington, Seattle, WA, USA
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Stacey A Cohen
- Division of Oncology, University of Washington, Seattle, WA, USA
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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22
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Xourafas D, Pawlik TM, Ejaz A, Dillhoff M, Abdel-Misih S, Tsung A, Cloyd JM. Impact of concomitant ablation on the perioperative outcomes of patients with colorectal liver metastases undergoing hepatectomy: a propensity score matched nationwide analysis. HPB (Oxford) 2019; 21:1079-1086. [PMID: 30718184 DOI: 10.1016/j.hpb.2018.12.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2018] [Accepted: 12/20/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Intraoperative ablation (IA) is often performed at the time of liver resection (LR) for colorectal liver metastases (CRLMs) but its impact on postoperative outcomes remains poorly understood. METHODS The ACS-NSQIP targeted hepatectomy database was used to identify patients who underwent LR vs LR + IA for CRLMs during 2014-2016. Perioperative outcomes were compared following propensity score match based on age, receipt of neoadjuvant therapy, operative approach, liver resection type, tumor diameter and number of metastases. RESULTS Among 1,384 patients, 692 (50%) underwent LR alone and 692 (50%) underwent LR + IA. After propensity score matching, overall morbidity (22% vs 13%, P < 0.0001) was increased among patients undergoing LR alone compared to LR + IA, whereas mortality did not differ (1.1% vs 0.8%, P=0.5911). On multivariable analysis, ASA class ≥3 (OR: 1.5, 95% CI: 1.06-2.3), preoperative biliary stent (OR: 3.5, 95% CI: 0.9-13.01), biliary reconstruction (OR: 5.02, 95% CI: 1.3-18.6), operative time > 245 minutes (OR: 1.8, 95% CI:1.3-2.4) and IA (OR:0.5, 95% CI:0.3-0.7) were associated with overall morbidity. CONCLUSIONS In this propensity matched nationwide analysis of patients undergoing LR for CRLM, the use of concomitant IA was associated with decreased postoperative morbidity compared to LR alone. These findings suggest that IA combined with LR is a safe approach that may expand the number of patients who are candidates for curative-intent surgical strategies.
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Affiliation(s)
- Dimitrios Xourafas
- Department of surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Aslam Ejaz
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Mary Dillhoff
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Sherif Abdel-Misih
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Allan Tsung
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
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Analysis of the feasibility of microwave ablation for colorectal liver metastases: a preliminary report. Wideochir Inne Tech Maloinwazyjne 2019; 15:30-35. [PMID: 32117483 PMCID: PMC7020727 DOI: 10.5114/wiitm.2019.86921] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Accepted: 06/06/2019] [Indexed: 01/28/2023] Open
Abstract
Introduction Colorectal liver metastasis is a challenge in the treatment of colorectal cancer and an important factor affecting the prognosis of patients. Currently, microwave ablation has gradually been applied for the treatment of liver cancers as a type of thermal ablation. However, there are no large-scale studies on the effectiveness of microwave ablation for colorectal liver metastases. Aim To investigate the efficacy of microwave ablation and liver resection for liver metastases from colorectal cancer, and to compare the prognosis between patients treated with microwave ablation and those in the SEER (Surveillance, Epidemiology, and End Results, National Cancer Institute) database. Material and methods We retrospectively analyzed the clinical data of 24 patients with colorectal liver metastasis who underwent radical colorectal cancer resection and liver microwave ablation (the MWA group) and 12 patients who received radical colorectal cancer resection and liver resection (the LR group). The complete ablation rate and complications after microwave ablation were observed. Survival analysis was performed for cases treated with liver resection and cases from the SEER database. Results A total of 53 tumors were ablated in the 24 patients who underwent radical colorectal cancer resection and liver microwave ablation; 52 tumors achieved complete ablation after the first ablation (98.1%). No serious complications occurred in the MWA group, and long-term survival was not significantly different between the MWA and other groups. Conclusions Microwave ablation for colorectal liver metastases avoids extensive liver resection while ensuring therapeutic efficacy; the operation is safe, feasible, and reproducible.
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Lee JE, Abuzar SM, Seo Y, Han H, Jeon Y, Park EJ, Baik SH, Hwang SJ. Oxaliplatin-loaded chemically cross-linked hydrogels for prevention of postoperative abdominal adhesion and colorectal cancer therapy. Int J Pharm 2019; 565:50-58. [DOI: 10.1016/j.ijpharm.2019.04.065] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 04/17/2019] [Accepted: 04/21/2019] [Indexed: 01/05/2023]
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Valdimarsson VT, Hellberg K, Brismar TB, Sparrelid E, Sturesson C. Repeat procedures for recurrent colorectal liver metastases: analysis of long-term liver regeneration and outcome. Cancer Manag Res 2019; 11:2617-2622. [PMID: 31118767 PMCID: PMC6497974 DOI: 10.2147/cmar.s191653] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Accepted: 01/21/2019] [Indexed: 12/31/2022] Open
Abstract
Background and aim: Repeat hepatectomy is increasingly performed for the management of recurrent colorectal liver metastases (CRLM). The aim of this study was to evaluate long-term functional liver volume (FLV) after a second hepatic procedure and to measure survival outcome. Methods: In this retrospective cohort study, patients treated for recurrent CRLM in the years 2005-2015 at two liver centers were included. Total FLV was calculated before the first procedure and before and after the second procedure. Overall survival was calculated. Results: Eighty-two patients were identified. The median follow-up was 53 (40-71) months from the first procedure. The median interval between first and second procedure was 13 (8-22) months. The initial FLV was 1584 (1313-1927) mL. The FLV was 1438 (1204-1896) mL after the first procedure and 1470 (1172-1699) mL after the second procedure (P<0.001). After the second procedure, a total of ten patients (12%) had a residual liver volume of less than 75% of the initial liver volume. The 5-year overall survival was 37 (26-54)% after the second procedure. Conclusion: Small changes in FLV were found after two hepatic procedures but with considerable inter-individual variation. Patients selected for a repeated hepatic procedure for recurrent CRLM had an acceptable survival.
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Affiliation(s)
- Valentinus T Valdimarsson
- Department of Clinical Sciences Lund, Surgery, Lund University, Skane University Hospital, Lund, Sweden
| | - Katarina Hellberg
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Torkel B Brismar
- Division of Radiology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Ernesto Sparrelid
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Christian Sturesson
- Department of Clinical Sciences Lund, Surgery, Lund University, Skane University Hospital, Lund, Sweden
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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Utility of Image Guidance in the Localization of Disappearing Colorectal Liver Metastases. J Gastrointest Surg 2019; 23:760-767. [PMID: 30680630 PMCID: PMC6717434 DOI: 10.1007/s11605-019-04106-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Accepted: 01/01/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Colorectal liver metastases that demonstrate a complete radiographic response during chemotherapy are increasingly common with advances in chemotherapy regimens and are described as disappearing liver metastases (DLMs). However, these DLMs often continue to harbor residual viable tumor. If these tumors are found in the operating room with ultrasound (US), they should be treated. The intraoperative sonographic visualization of these lesions, however, can be hindered by chemotherapy-associated liver parenchyma changes. The objective of this study was to evaluate the use of an intraoperative image guidance system, Explorer (Analogic Corporation, Peabody, MA), to aid surgeons in the identification of DLMs initially undetected by US alone. STUDY DESIGN In a single-arm prospective trial, patients with colorectal liver metastases undergoing liver resection and/or ablation with one or more DLMs during neoadjuvant chemotherapy were enrolled. Intraoperatively, DLMs were localized with conventional US. Any DLM not found by conventional US was re-evaluated with the image guidance system. The primary outcome was the proportion of sonographically occult DLMs subsequently located by image-guided US. RESULTS Between April 2016 and November 2017, 25 patients with 61 DLMs were enrolled. Thirty-eight DLMs (62%) in 14 patients (56%) were not identified with US alone. Six (16%) DLMs in five patients (36%) were subsequently located with assistance of the image guidance system. The image guidance changed the intraoperative surgical plan in four of these patients. CONCLUSIONS Image guidance can aid surgeons in the identification of initially sonographically occult DLMs and facilitate the complete surgical clearance of all sites of liver disease.
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27
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Aguilar-Medina M, Avendaño-Félix M, Lizárraga-Verdugo E, Bermúdez M, Romero-Quintana JG, Ramos-Payan R, Ruíz-García E, López-Camarillo C. SOX9 Stem-Cell Factor: Clinical and Functional Relevance in Cancer. JOURNAL OF ONCOLOGY 2019; 2019:6754040. [PMID: 31057614 PMCID: PMC6463569 DOI: 10.1155/2019/6754040] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 02/21/2019] [Indexed: 12/15/2022]
Abstract
Transcriptional and epigenetic embryonic programs can be reactivated in cancer cells. As result, a specific subset of undifferentiated cells with stem-cells properties emerges and drives tumorigenesis. Recent findings have shown that ectoderm- and endoderm-derived tissues continue expressing stem-cells related transcription factors of the SOX-family of proteins such as SOX2 and SOX9 which have been implicated in the presence of cancer stem-like cells (CSCs) in tumors. Currently, there is enough evidence suggesting an oncogenic role for SOX9 in different types of human cancers. This review provides a summary of the current knowledge about the involvement of SOX9 in development and progression of cancer. Understanding the functional roles of SOX9 and clinical relevance is crucial for developing novel treatments targeting CSCs in cancer.
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Affiliation(s)
- Maribel Aguilar-Medina
- Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Culiacán, Sinaloa, Mexico
| | - Mariana Avendaño-Félix
- Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Culiacán, Sinaloa, Mexico
| | - Erik Lizárraga-Verdugo
- Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Culiacán, Sinaloa, Mexico
| | - Mercedes Bermúdez
- Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Culiacán, Sinaloa, Mexico
| | | | - Rosalío Ramos-Payan
- Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Culiacán, Sinaloa, Mexico
| | - Erika Ruíz-García
- Laboratorio de Medicina Traslacional y Departamento de Tumores Gastro-Intestinales, Instituto Nacional de Cancerología. CDMX, Mexico
| | - César López-Camarillo
- Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, CDMX, Mexico
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Mor E, Al-Kurd A, Yaacov AB, Aderka D, Nissan A, Ariche A. Surgical outcomes of two-stage hepatectomy for colorectal liver metastasis: comparison to a benchmark procedure. Hepatobiliary Surg Nutr 2019; 8:29-36. [PMID: 30881963 DOI: 10.21037/hbsn.2018.12.02] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Background Two-stage hepatectomy (TSH) with portal vein embolization (PVE) is associated with high morbidity and mortality and may result in liver failure due to insufficient future liver remnant. The objectives of this investigation were to evaluate the short-term outcomes of patients with colorectal cancer liver metastasis who underwent TSH with PVE, and to critically review the selection criteria for TSH-PVE. Methods A retrospective review of all patients who were operated due to bi-lobar CRLM during the years 2007-2017 was performed. Patients who underwent TSH-PVE were compared to those who underwent right hepatectomy (RH) only. Results Twenty-nine patient underwent TSH, 25 of whom (86.2%) completed both stages. These patients demonstrated a major complication rate of 17%, and a 90-day mortality rate of 3.4%. Most complications (80%) were related to the colonic resection, and one patient developed liver failure. Patients who suffered complications had a trend towards more baseline comorbidities and more liver lesions. Ablative techniques were utilized in 76%. When compared to 35 patients who underwent sole RH, no significant difference was demonstrated in major complication rate (20%) or mortality (0%). Conclusions TSH is a relatively safe procedure in selected patients. Ablative techniques can reduce the occurrence of liver insufficiency and should be used liberally when possible. Factors such as number of lesions, comorbidities and the timing of colonic resection should be considered and evaluated in order to improve the outcomes of the procedure.
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Affiliation(s)
- Eyal Mor
- Department of General and Oncological Surgery, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Abbas Al-Kurd
- Department of Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Almog Ben Yaacov
- Department of General and Oncological Surgery, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Dan Aderka
- Department of Oncology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Aviram Nissan
- Department of General and Oncological Surgery, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Arie Ariche
- Department of Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.,Department of Hepatobiliary Surgery, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
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Harada T, Matsumoto S, Hirota S, Kimura H, Fujii S, Kasahara Y, Gon H, Yoshida T, Itoh T, Haraguchi N, Mizushima T, Noda T, Eguchi H, Nojima S, Morii E, Fukumoto T, Obika S, Kikuchi A. Chemically Modified Antisense Oligonucleotide Against ARL4C Inhibits Primary and Metastatic Liver Tumor Growth. Mol Cancer Ther 2019; 18:602-612. [PMID: 30647122 DOI: 10.1158/1535-7163.mct-18-0824] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 10/26/2018] [Accepted: 01/10/2019] [Indexed: 11/16/2022]
Abstract
ADP-ribosylation factor-like 4c (ARL4C) is identified as a small GTP-binding protein, which is expressed by Wnt and EGF signaling and plays an important role in tubulogenesis of cultured cells and the ureters. ARL4C is little expressed in adult tissues, but it is highly expressed in lung cancer and colorectal cancer and shown to represent a molecular target for cancer therapy based on siRNA experiments. This study revealed that ARL4C is highly expressed in primary hepatocellular carcinoma (HCC) tumors and colorectal cancer liver metastases, and that ARL4C expression is associated with poor prognosis for these cancers. Chemically modified antisense oligonucleotides (ASO) against ARL4C effectively reduced ARL4C expression in both HCC and colorectal cancer cells and inhibited proliferation and migration of these cancer cells in vitro ARL4C ASOs decreased the PIK3CD mRNA levels and inhibited the activity of AKT in HCC cells, suggesting that the downstream signaling of ARL4C in HCC cells is different from that in lung and colon cancer cells. In addition, subcutaneous injection of ARL4C ASO was effective in reducing the growth of primary HCC and metastatic colorectal cancer in the liver of immunodeficient mice. ARL4C ASO accumulated in cancer cells more efficiently than the surrounding normal cells in the liver and decreased ARL4C expression in the tumor. These results suggest that ARL4C ASO represents a novel targeted nucleic acid medicine for the treatment of primary and metastatic liver cancers.
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Affiliation(s)
- Takeshi Harada
- Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Shinji Matsumoto
- Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Suguru Hirota
- Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Hirokazu Kimura
- Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Shinsuke Fujii
- Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yuuya Kasahara
- Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.,National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
| | - Hidetoshi Gon
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Toshihiko Yoshida
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Tomoo Itoh
- Division of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Naotsugu Haraguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Tsunekazu Mizushima
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Satoshi Nojima
- Department of Pathology, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Eiichi Morii
- Department of Pathology, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Takumi Fukumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Satoshi Obika
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.,National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
| | - Akira Kikuchi
- Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Osaka, Japan.
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Imajo K, Tomeno W, Kanezaki M, Honda Y, Kessoku T, Ogawa Y, Yoshida K, Yoneda M, Kirikoshi H, Ono M, Kaneta T, Inoue T, Teratani T, Saito S, Nakajima A. New microwave ablation system for unresectable liver tumors that forms large, spherical ablation zones. J Gastroenterol Hepatol 2018; 33:2007-2014. [PMID: 29851164 DOI: 10.1111/jgh.14294] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 04/21/2018] [Accepted: 05/15/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM The aim of this study was to assess the efficacy of a new microwave ablation (MWA) system, the Emprint Ablation System, for the ablation of unresectable large liver tumors (≥ 30 mm). METHODS Twenty-one hepatic tumors (mean diameter, 34.7 mm) from 21 patients who underwent percutaneous MWA were included in this cross-sectional study. A volume analyzer based on computed tomography imaging was used for all patients within the month before and month after the procedure to evaluate the shape and volume of ablation zones. In addition, computed tomography imaging was performed again 3 months after the procedure to evaluate the presence of residual tumors and local recurrence. RESULTS Mean ablation time was 11.3 min, and mean overall procedure time was 33.4 min. An ablated adrenal gland-induced Takotsubo (stress) cardiomyopathy occurred immediately after MWA as a major complication in one patient. Roundness index A, B, and C presented a mean value of 0.94, 0.94, and 1.01, respectively (all values near 1 is a perfect sphere), indicating that a spherical ablation zone was achieved. The mean ablation volume was larger than the volume of tumors (24.5 vs 41.7 cm3 ). Residual tumors were confirmed in only 4.8% of tumors after a single ablation session. There was no local recurrence. CONCLUSIONS In our experience, the new MWA system provides an effective treatment option for unresectable large liver tumors. However, to ablate the liver tumors safely, it is necessary to consider the surrounding organs, such as the adrenal glands.
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Affiliation(s)
- Kento Imajo
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Wataru Tomeno
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Mineo Kanezaki
- Department of Gastroenterology, Kanto Medical Center Tokyo, Tokyo, Japan
| | - Yasushi Honda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Takaomi Kessoku
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yuji Ogawa
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Keisuke Yoshida
- Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Hiroyuki Kirikoshi
- Department of Clinical Laboratory, Yokohama City University Hospital, Yokohama, Japan
| | - Masafumi Ono
- Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi, Japan
| | - Tomohiro Kaneta
- Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Tomio Inoue
- Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Takuma Teratani
- Department of Gastroenterology, Kanto Medical Center Tokyo, Tokyo, Japan
| | - Satoru Saito
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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Ishida K, Tamura A, Kato K, Uesugi N, Osakabe M, Eizuka M, Hasegawa Y, Nitta H, Otsuka K, Sasaki A, Ehara S, Sugai T. Correlation between CT morphologic appearance and histologic findings in colorectal liver metastasis after preoperative chemotherapy. Abdom Radiol (NY) 2018; 43:2991-3000. [PMID: 29616287 DOI: 10.1007/s00261-018-1588-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
PURPOSE Radiological evaluation of the efficacy of preoperative chemotherapy for colorectal liver metastasis (CRLM) is the most important tool for determining treatment strategies. The aim of this study was to identify a correlation between morphologic appearance on computed tomography (CT) and histologic findings of CRLM after preoperative chemotherapy. METHODS We examined 47 patients who had undergone a first hepatic resection for CRLM after preoperative chemotherapy and had received contrast-enhanced CT scans. We assessed the morphologic appearance of the overall attenuation based on metastases changing from heterogeneous to mixed and homogenous lesions, the tumor-liver interface, and the peripheral rim enhancement on CT. Histologic parameters included usual necrosis (UN), infarct-like necrosis (ILN), three-zonal change, dangerous halo, mucous lake, shape of ILN, dominant type of necrosis, and presence of viable tumor cells. The relationship between morphologic appearance and histologic findings was evaluated. RESULTS CT overall attenuation revealed that UN predominance was more common in the heterogeneous group than in the mixed and homogeneous groups (P = 0.011). The frequency of ILN increased sequentially from ill-defined to variable and sharp at the tumor-liver interface (P = 0.038), and the frequency of UN decreased sequentially from present to partially resolved and completely resolved in the peripheral rim enhancement (P = 0.023). The histologic presence of viable tumor cells was closely associated with the tumor-liver interface (P = 0.0003) and the peripheral rim enhancement (P = 0.004). CONCLUSIONS CT morphologic appearance of CRLM after preoperative chemotherapy is correlated with histologic findings regarding necrosis.
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Hirata F, Ishiyama K, Tanaka Y, Kobayashi T, Hashimoto M, Saeki Y, Ishida N, Taguchi K, Tanaka J, Arihiro K, Ohdan H, Hiroshima Surgical Study Group of Clinical Oncology (HiSCO). Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis. Ann Gastroenterol Surg 2018; 2:383-393. [PMID: 30238080 PMCID: PMC6139723 DOI: 10.1002/ags3.12195] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 05/28/2018] [Accepted: 06/26/2018] [Indexed: 12/22/2022] Open
Abstract
AIM We investigated the chemotherapy effect of resectable colorectal cancer with liver metastasis (CRLM) on the function of intrahepatic immune cells. METHODS We classified patients into adjuvant chemotherapy (bevacizumab+CapeOX) after hepatectomy group (group A) and neoadjuvant chemotherapy followed by hepatectomy group (group B), and collected peripheral blood mononuclear cells (PBMC) and liver mononuclear cells (LMNC) to ascertain phenotypic and functional differences. RESULTS There were no significant differences in lymphocyte fractions of either PBMC or LMNC between groups, except for the significantly lower percentage of natural killer (NK) cells in LMNC in group B than in group A. Significantly higher percentage of natural-killer group 2, member D (NKG2D)- positive NK cells in PBMC and percentage of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-, NKp30-, and signal regulatory protein β (SIRPβ)-positive NK cells in LMNC were found in group B. Furthermore, significantly higher expressions of NKG2D and SIRPβ in peripheral blood NK cells and of NKp46 and CD122 in liver NK cells were found in group B. When LMNC were incubated with interleukin (IL)-2 in vitro, no difference was observed in the expression of these molecules in NK cells between groups. Consistently, there was no difference in the cytotoxic activity of those LMNC against a colon adenocarcinoma cell line between groups. CONCLUSION Colorectal cancer with liver metastasis patients treated with neoadjuvant chemotherapy showed enhanced expression of activation markers on peripheral blood and liver NK cells in comparison with patients who did not receive therapy; however, the difference in those function remains unclear. These results suggest that neoadjuvant chemotherapy does not have a negative impact on intrahepatic immune cells in resectable CRLM patients.
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Affiliation(s)
- Fumihiro Hirata
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health SciencesHiroshima UniversityHiroshimaJapan
| | - Kohei Ishiyama
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health SciencesHiroshima UniversityHiroshimaJapan
- Department of SurgeryNational Hospital Organization Kure Medical Center and Chugoku Cancer CenterHiroshimaJapan
| | - Yuka Tanaka
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health SciencesHiroshima UniversityHiroshimaJapan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health SciencesHiroshima UniversityHiroshimaJapan
| | - Masakazu Hashimoto
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health SciencesHiroshima UniversityHiroshimaJapan
| | - Yoshihiro Saeki
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health SciencesHiroshima UniversityHiroshimaJapan
| | - Nobuki Ishida
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health SciencesHiroshima UniversityHiroshimaJapan
| | - Kazuhiro Taguchi
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health SciencesHiroshima UniversityHiroshimaJapan
| | - Junko Tanaka
- Department of EpidemiologyInfectious Disease Control and PreventionGraduate School of Biomedical & Health SciencesHiroshima UniversityHiroshimaJapan
| | - Koji Arihiro
- Department of Anatomical PathologyHiroshima University HospitalHiroshimaJapan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health SciencesHiroshima UniversityHiroshimaJapan
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McCluney SJ, Giakoustidis AA, Segler A, Bissel J, Miller RL, Valente R, Hutchins RR, Abraham A, Bhattacharya S, Kocher HM. Predicting complications in hepatic resection for colorectal liver metastasis: the lymphocyte-to-monocyte ratio. ANZ J Surg 2018; 88:E782-E786. [PMID: 30014560 DOI: 10.1111/ans.14725] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Revised: 05/01/2018] [Accepted: 05/05/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Colorectal cancer is one of the most common malignancies worldwide; whilst approximately 20% of patients have hepatic disease at presentation. Hepatic resection remains the gold standard of care; however, it is associated with significant morbidity. We sought to establish whether the lymphocyte-to-monocyte ratio (LMR) could help predict post-operative complications, thus improving patient outcomes. METHODS We performed a retrospective cohort study of patients undergoing hepatic resection at a single centre. Baseline demographics and complications within 30 days following surgery were recorded. White blood cell counts and C-reactive protein (CRP) were recorded pre-operatively, and until post-operative day 7. RESULTS A total of 188 operations were included. About 47.3% of resections had a complicated recovery, of which 31.46% were major. The median LMR was 1.29 across the cohort, 1.60 for uncomplicated procedures, 1.14 for those with complications and 0.85 in major complications. For detecting major complications versus an uncomplicated recovery, median LMR was the best parameter (area under the curve 0.78), whilst it was the only parameter to accurately predict such complications within 48 hours of surgery (area under the curve 0.72 on day 1). It was consistently the most accurate parameter at detecting uncomplicated versus complicated recovery, minor versus major complications, and major complications versus an uncomplicated recovery, at numerous timepoints over the post-operative period. CONCLUSION The LMR appears better at predicting complications following hepatic resection for colorectal liver metastases, as opposed to conventionally measured parameters.
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Affiliation(s)
- Simon J McCluney
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK.,Barts Cancer Institute, Queen Mary University of London, London, UK
| | - Alexandros A Giakoustidis
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Angela Segler
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Juliane Bissel
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Robert L Miller
- The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Roberto Valente
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Robert R Hutchins
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Ajit Abraham
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Satyajit Bhattacharya
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Hemant M Kocher
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK.,Barts Cancer Institute, Queen Mary University of London, London, UK
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Curley SA, Vecchio R. New Trends in the Surgical Treatment of Colorectal Cancer Liver Metastases. TUMORI JOURNAL 2018; 84:281-8. [PMID: 9678609 DOI: 10.1177/030089169808400301] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Colorectal cancer is one of the most common solid tumors affecting people around the world. A significant proportion of patients with colorectal cancer will develop or will present with liver metastases. In some of these patients, the liver is the only site of metastatic disease. Thus, surgical treatment approaches are an appropriate and important treatment option in patients with liver-only colorectal cancer metastases. Resection of colorectal cancer liver metastases can produce long-term survival in selected patients, but the efficacy of liver resection as a solitary treatment is limited by two factors. First, a minority of patients with liver metastases have resectable disease. Second, the majority of patients who undergo successful liver resection for colorectal cancer metastases develop recurrent disease in the liver, extrahepatic sites, or both. In this paper, in addition to the results of liver resection for colorectal cancer metastases, we will review the results of cryoablation, heat ablation, and hepatic arterial chemotherapy using a surgically implanted pump. Each of these surgical treatment modalities can produce long-term survival in a subset of patients with liver-only colorectal cancer metastases, whereas systemic chemotherapy used alone rarely results in long-term survival in these patients. While surgical treatments provide the best chance for long-term survival or, in some cases, the best palliation in patients with colorectal cancer liver metastases, it is clear that further improvements in patient outcome will require multimodality therapy regimens.
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Affiliation(s)
- S A Curley
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA
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35
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Bertuccelli M, Falcone A, Campoccia S, Conti M, Brunetti I, Caramella D, Giulianotti PC, Mosca F, Bartolozzi C, Conte PF. Intrahepatic Chemotherapy with Floxuridine, Leucovorin and Dexamethasone in Continuous Infusion and Mitomycin-c Bolus in Unresectable Hepatic Metastases from Colorectal Cancer: A Phase II Study. TUMORI JOURNAL 2018; 85:473-7. [PMID: 10774568 DOI: 10.1177/030089169908500609] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Background Intrahepatic continuous infusion FUDR induces a 50% response rate in patients with hepatic metastases from colorectal cancer. Lower rates have been observed in pretreated patients. The combination of floxuridine plus leucovorin has obtained over 70% responses, with high hepatic toxicity. The use of dexamethasone can decrease hepatic toxicity. A randomized study reported an increase in response rate and a decrease in hepatic toxicity in a group of patients treated with floxuridine plus dexamethasone compared to a group receiving only floxuridine. Moreover, the combination of mitomycin C, carmustine and floxuridine is also effective in pretreated patients. Methods On such premises, since July 1993 we have treated 39 patients affected by unresectable hepatic metastases from colon carcinoma (26 patients) and rectal carcinoma (13 patients) with the combination continuous infusion of floxuridine (0.20 mg/kg per day) + leucovorin (7.5 mg/m2/day) + dexamethasone (20 mg on days 1 to 14) and bolus mitomycin C (10 mg/m2 on day 1) via the hepatic artery. Cycles were administered every four weeks. There were as 28 males and 11 females, with a median age of 64 years (range, 39-75) and a median PS = 0. Twenty-two patients were pretreated with systemic chemotherapy including 5-fluorouracil plus leucovorin. Total number of cycles was 189, with a median of 6 cycles per patient (range, 1-12). Results Of 39 patients 37 were assessable for response (2 patients were not assessable because they stopped chemotherapy for occlusion of the catheter after the first cycle). There were 3 complete responses (1 in a naive patient and 2 in pretreated patients), 16 partial responses (11 in pretreated patients and 5 in chemonaive patients), 4 minor responses, 4 stable disease and 10 progressive disease. The overall response rate was 51.3% (95 CI, 51.3-86.7%). Median time to progression was 6 months (range, 1-34+). Overall survival was 18 months (range, 1-34+). Of 39 patients, 36 were assessable for toxicity (WHO) (3 patients died after the first cycle for progression of disease): diarrhea and nausea-vomiting grade 3-4 occurred respectively in 15 (41%) and 3 patients (8%); hepatic toxicity was mild. Conclusions The treatment we used showed an elevated activity in liver metastases from colorectal cancer even in patients pretreated and resistant to systemic chemotherapy, although toxicity grade 3-4 diarrhea occurred in approximately 40% of the patients.
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Affiliation(s)
- M Bertuccelli
- Sezione di Oncologia Medica, Ospedale di Livorno, Italy
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Kingham TP, Pak LM, Simpson AL, Leung U, Doussot A, D’Angelica MI, DeMatteo RP, Allen PJ, Jarnagin WR. 3D image guidance assisted identification of colorectal cancer liver metastases not seen on intraoperative ultrasound: results from a prospective trial. HPB (Oxford) 2018; 20:260-267. [PMID: 28935452 PMCID: PMC6717433 DOI: 10.1016/j.hpb.2017.08.035] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 08/21/2017] [Accepted: 08/31/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Neoadjuvant treatment of colorectal liver metastases has become increasingly common, and while effective, often renders small metastases difficult to visualize on intraoperative US. The objective of this study was to determine the utility of a 3D image-guidance system in patients with intraoperative sonographically-occult CRLM. METHODS 50 patients with at least one CRLM ≤ 1.5 cm were enrolled in this prospective trial of an FDA-approved Explorer image-guidance system. If the tumor(s) seen on preoperative imaging were not identified with intraoperative US, Explorer was used to target the US examination to the involved area for a more focused assessment. The primary endpoint was the proportion of cases with sonographically-occult metastases identified using Explorer. RESULTS Forty-eight patients with preoperative scans within eight weeks of surgery were included for analysis. Forty-six patients were treated with preoperative chemotherapy (median 4 months, range 2-24 months). Overall, 22 sonographically-occult tumors in 14 patients were interrogated by Explorer, of which 15 tumors in 10 patients were located with image-guidance assistance. The only difference between patients with tumors not identified on US and those who did was the number of tumors (median 3 vs. 2, p = 0.018). CONCLUSION 3D image-guidance can assist in identifying small CRLM, particularly after treatment with chemotherapy. TRIAL REGISTRATION ClinicalTrials.gov, NCT02806037, https://clinicaltrials.gov/ct2/show/NCT02806037.
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37
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Moon A, Do SI, Kim HS, Kim YW. Downregulation of osteoprotegerin expression in metastatic colorectal carcinoma predicts recurrent metastasis and poor prognosis. Oncotarget 2018; 7:79319-79326. [PMID: 27764814 PMCID: PMC5346716 DOI: 10.18632/oncotarget.12686] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Accepted: 09/30/2016] [Indexed: 12/18/2022] Open
Abstract
We recently reported the downregulation of osteoprotegerin expression in primary colorectal carcinoma and its significant association with aggressive oncogenic behavior, which suggest that this process contributes to colorectal carcinoma development and progression. In this study, we used immunohistochemical staining to evaluate osteoprotegerin expression in 81 colorectal liver metastasis tissue samples and investigated its possible association with the clinicopathological characteristics and outcomes of patients with colorectal liver metastasis. These tissues exhibited significantly reduced expression of osteoprotegerin compared to primary colorectal carcinomas and normal colorectal mucosa. This reduced expression was significantly associated with the extent of colorectal liver metastasis, including multiplicity of metastatic tumors, involvement of the bilateral hepatic lobes, and higher histological grade. In addition, reduced osteoprotegerin expression was an independent significant predictor of recurrent liver metastasis and prognostic factor for reduced patient survival. These findings suggest that osteoprotegerin expression may be a novel predictor of recurrent liver metastasis and a prognostic biomarker in patients with colorectal liver metastasis. Patients harboring colorectal liver metastasis with reduced osteoprotegerin expression should be carefully monitored after hepatic resection for colorectal liver metastasis to enable early detection of potentially resectable metastatic recurrences.
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Affiliation(s)
- Ahrim Moon
- Department of Pathology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon-si, Gyeonggi-do, Republic of Korea
| | - Sung-Im Do
- Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hyun-Soo Kim
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Youn-Wha Kim
- Department of Pathology, Kyung Hee University School of Medicine, Seoul, Republic of Korea
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Omichi K, Shindoh J, Cloyd JM, Mizuno T, Chun YS, Conrad C, Aloia TA, Tzeng CWD, Vauthey JN. Liver resection is justified for patients with bilateral multiple colorectal liver metastases: A propensity-score-matched analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2018; 44:122-129. [PMID: 29208318 PMCID: PMC5742306 DOI: 10.1016/j.ejso.2017.11.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Revised: 10/20/2017] [Accepted: 11/08/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Increasingly, patients with multiple colorectal liver metastases (CLM) are surgically treated. Some studies have shown that patients with bilobar and unilobar multiple CLM have similar outcomes, but other have shown that patients with bilobar CLM have worse outcomes after resection. We aimed to compare clinical outcomes of surgical treatment of bilobar and unilobar CLM using propensity score matching. METHODS The single-institution study included patients who underwent hepatectomy for ≥3 histologically confirmed CLM during 1998-2014. Clinicopathologic characteristics and long-term outcomes were compared between patients with bilobar and unilobar CLM in a propensity-score-adjusted cohort. RESULTS A total of 473 patients met the inclusion criteria, 271 (57%) with bilobar and 202 (43%) with unilobar CLM. In the propensity-score-matched population (bilobar, 170; unilobar, 170), no differences were observed according to the distribution of CLM except for a greater frequency of concomitant ablation, and R1 resection in the bilobar group. There was no difference between the bilobar and unilobar groups in 5-year overall survival rates (46% and 49%, respectively; P = 0.740) or 3-year recurrence-free survival rates (21% and 24%, respectively; P = 0.674). CONCLUSIONS Tumor distribution may not affect the curability of surgery for multiple CLM. Liver resection would be justified for selected patients with bilobar CLM.
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Affiliation(s)
- Kiyohiko Omichi
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Junichi Shindoh
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Hepatobiliary-Pancreatic Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo, Japan
| | - Jordan M Cloyd
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Takashi Mizuno
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Claudius Conrad
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Thomas A Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Feng Q, Wei Y, Ren L, Zheng P, Yu Y, Ye Q, Ding J, Chen J, Chang W, Zhong Y, Zhu D, Lin Q, Yang L, Qin X, Xu J. Efficacy of continued cetuximab for unresectable metastatic colorectal cancer after disease progression during first-line cetuximab-based chemotherapy: a retrospective cohort study. Oncotarget 2017; 7:11380-96. [PMID: 26863631 PMCID: PMC4905480 DOI: 10.18632/oncotarget.7193] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Accepted: 01/23/2016] [Indexed: 12/22/2022] Open
Abstract
This study assessed second-line continued use of cetuximab for treatment of unresectable metastatic colorectal cancer (mCRC) after disease progression during first-line cetuximab-based therapy. Consecutive patients with wild-type KRAS exon 2 and unresectable mCRC were retrospectively enrolled after disease progression during first-line cetuximab-based chemotherapy. Second-line continued cetuximab plus changed chemotherapy (cetuximab continuation group, n = 102) was compared with changed chemotherapy only (chemotherapy only group, n = 96) with respect to treatment efficacy and safety endpoints. NRAS and other KRAS genotypes were also detected as a post hoc analysis. The cetuximab continuation group showed better progression-free survival (median, 6.3 vs. 4.5 months, P = 0.004), overall survival (median, 17.3 vs. 14.0 months, P < 0.001) and disease control rate (70.6% vs. 53.1%, P = 0.011), and a potentially better overall response rate (18.6% vs. 9.4%, P = 0.062) than the chemotherapy only group. These benefits were seen mainly in patients with all RAS wild-type and exhibiting first-line early tumor shrinkage (ETS). For patients with other RAS mutations or who did not achieve first-line ETS, there was no difference between the two groups. These findings suggest that for patients with all RAS wild-type and unresectable mCRC who had disease progression during first-line cetuximab-based treatment, second-line continued cetuximab is effective. Moreover, ETS during first-line cetuximab-based treatment may be predictive of the efficacy of second-line continued cetuximab.
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Affiliation(s)
- Qingyang Feng
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ye Wei
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Li Ren
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Peng Zheng
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yiyi Yu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qinghai Ye
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jianyong Ding
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jingwen Chen
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenju Chang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yunshi Zhong
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dexiang Zhu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qi Lin
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Liangliang Yang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xinyu Qin
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jianmin Xu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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Walker TLJ, Bamford R, Finch-Jones M. Intraoperative ultrasound for the colorectal surgeon: current trends and barriers. ANZ J Surg 2017; 87:671-676. [PMID: 28771975 DOI: 10.1111/ans.14124] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Revised: 05/12/2017] [Accepted: 05/28/2017] [Indexed: 12/14/2022]
Abstract
Up to two thirds of patients diagnosed with colorectal cancer (CRC) develop colorectal liver metastases (CRLMs) and one quarter of patients present with synchronous metastases. Early detection of CRLM widens the scope of potential treatment. Surgery for CRLM offers the best chance of a cure. Current preoperative staging of CRC relies on computerized tomography and magnetic resonance imaging. Intraoperative ultrasound (IOUS) scans and contrast-enhanced IOUS (CE-IOUS) have been demonstrated to detect additional metastases not seen on routine preoperative imaging. IOUS is not widely used by colorectal surgeons during primary resection for CRC. Confident use of IOUS/CE-IOUS during primary resection of CRC may improve decision-making by providing the most sensitive form of liver staging even when compared with magnetic resonance imaging. This may be particularly important in the era of laparoscopic resections, where the colorectal surgeon loses the opportunity to palpate the liver. There are several implied barriers to the routine use of IOUS/CE-IOUS by colorectal surgeons. These include time pressure, familiarity with techniques, a perceived learning curve, cost implications and limitation of the modality due to operator variations. Inclusion of IOUS in the training of colorectal surgeons and further investigation of potential benefits of IOUS/CE-IOUS could potentially reduce these barriers, enabling usage during primary resection for CRC to become more widespread.
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Affiliation(s)
- Thomas L J Walker
- Department of Hepato-Pancreato-Biliary Surgery, Bristol Royal Infirmary, University Hospitals Bristol, Bristol, UK
| | - Richard Bamford
- Department of Hepato-Pancreato-Biliary Surgery, Bristol Royal Infirmary, University Hospitals Bristol, Bristol, UK
| | - Margaret Finch-Jones
- Department of Hepato-Pancreato-Biliary Surgery, Bristol Royal Infirmary, University Hospitals Bristol, Bristol, UK
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Yang Q, Tang P, He G, Ge S, Liu L, Zhou X. Hemocoagulase Combined with Microbubble-Enhanced Ultrasound Cavitation for Augmented Ablation of Microvasculature in Rabbit VX2 Liver Tumors. ULTRASOUND IN MEDICINE & BIOLOGY 2017; 43:1658-1670. [PMID: 28545858 DOI: 10.1016/j.ultrasmedbio.2017.03.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 03/20/2017] [Accepted: 03/21/2017] [Indexed: 06/07/2023]
Abstract
We investigated a new method for combining microbubble-enhanced ultrasound cavitation (MEUC) with hemocoagulase (HC) atrox. Our goal was to induce embolic effects in the vasculature and combine these with an anti-angiogenic treatment strategy. Fourteen days after being implanted with a single slice of the liver VX2 tumor, rabbits were randomly divided into five groups: (i) a control group injected intra-venously with saline using a micropump; (ii) a group given only an injection of HC; (iii) a group treated only with ultrasound cavitation; (iv) a group treated with MEUC; (v) a group treated with MEUC + HC. Contrast-enhanced ultrasound was performed before treatment and 1 h and 7 d post-treatment to measure tumor size, enhancement and necrosis range. QontraXt software was used to determine the time-intensity curve of tumor blood perfusion and microvascular changes. At 1 h and 7 d after treatment with MEUC + HC, the parameters of the time-intensity curve, which included peak value, regional blood volume, regional blood flow and area under the curve value and which were measured using contrast-enhanced ultrasound, were significantly lower than those of the other treatment groups. The MEUC + HC treatment group exhibited significant growth inhibition relative to the ultrasound cavitation only, HC and MEUC treatment groups. No damage was observed in the surrounding normal tissues. These results support the feasibility of reducing the blood perfusion of rabbit VX2 liver tumors using a new method that combines MEUC and HC.
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Affiliation(s)
- Qian Yang
- Department of Ultrasound, Xijing Hospital, Xi'an, China
| | - Peng Tang
- Department of Orthopedics and Rehabilitation, China Rehabilitation Research Center, Beijing Charity Hospital, Beijing, China
| | - Guangbin He
- Department of Ultrasound, Xijing Hospital, Xi'an, China
| | - Shuping Ge
- The Heart Center, St. Christopher's Hospital for Children & Drexel University College of Medicine, Philadelphia, Pennsylvania, USA; Deborah Heart and Lung Center, Browns Mills, New Jersey, USA
| | - Liwen Liu
- Department of Ultrasound, Xijing Hospital, Xi'an, China.
| | - Xiaodong Zhou
- Department of Ultrasound, Xijing Hospital, Xi'an, China
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Colorectal Cancer Surveillance: What Is the Optimal Frequency of Follow-up and Which Tools Best Predict Recurrence? CURRENT COLORECTAL CANCER REPORTS 2017. [DOI: 10.1007/s11888-017-0382-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Deng R, Wu H, Ran H, Kong X, Hu L, Wang X, Su Q. Glucose-derived AGEs promote migration and invasion of colorectal cancer by up-regulating Sp1 expression. Biochim Biophys Acta Gen Subj 2017; 1861:1065-1074. [PMID: 28237576 DOI: 10.1016/j.bbagen.2017.02.024] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Revised: 01/29/2017] [Accepted: 02/21/2017] [Indexed: 01/11/2023]
Abstract
It is well established that the risk of colorectal cancer (CRC) is significantly increased in diabetic patients. As one of main forms of the advanced glycation end products (AGEs) that accumulate in vivo, glucose-derived AGEs play an important role in the pathogenesis of diabetic complications and may contribute to CRC progression. However, to date, both the contribution of glucose-derived AGEs to the course of CRC and the underlying mechanism are unclear. In the present study, the concentration of glucose-derived AGEs in the serum and tumor tissue of patients with CRC increased. A clinical data analysis demonstrated that the expression of the receptor for AGEs (RAGE), Specificity Protein 1 (Sp1), and matrix metallopeptidase -2 (MMP2) was significantly higher in cancerous tissues compared with non-tumor tissue in Chinese Han patients with CRC and that RAGE expression was closely associated with lymph node metastasis and TNM stage. Furthermore, in vivo and in vitro experiments showed that AGEs promoted invasion and migration of colorectal cancer, and the AGEs treatment increased the expression of RAGE, Sp1, and MMP2 in a dose-dependent manner. A RAGE blocking antibody and an Sp1-specific siRNA attenuated the AGE-induced effects. Moreover, the AGEs treatment increased the phosphorylation of ERK, and reducing the phosphorylation level of ERK by MEK1/2 inhibitor decreased the expression of Sp1. In conclusion, glucose-derived AGEs promote the invasion and metastasis of CRC partially through the RAGE/ERK/SP1/MMP2 cascade. These findings may provide an explanation for the poor prognoses of colorectal cancer in diabetic patients.
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Affiliation(s)
- Ruyuan Deng
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665, Kong Jiang Road, Shanghai 200092, China
| | - Huo Wu
- Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Hui Ran
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665, Kong Jiang Road, Shanghai 200092, China
| | - Xiang Kong
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665, Kong Jiang Road, Shanghai 200092, China
| | - Lei Hu
- Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xiao Wang
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
| | - Qing Su
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665, Kong Jiang Road, Shanghai 200092, China.
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Qiao G, Qin J, Kunda N, Calata JF, Mahmud DL, Gann P, Fu YX, Rosenberg SA, Prabhakar BS, Maker AV. LIGHT Elevation Enhances Immune Eradication of Colon Cancer Metastases. Cancer Res 2017; 77:1880-1891. [PMID: 28249900 DOI: 10.1158/0008-5472.can-16-1655] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Revised: 12/28/2016] [Accepted: 01/20/2017] [Indexed: 01/23/2023]
Abstract
The majority of patients with colon cancer will develop advanced disease, with the liver being the most common site of metastatic disease. Patients with increased numbers of tumor-infiltrating lymphocytes in primary colon tumors and liver metastases have improved outcomes. However, the molecular factors that could empower antitumor immune responses in this setting remain to be elucidated. We reported that the immunostimulatory cytokine LIGHT (TNFSF14) in the microenvironment of colon cancer metastases associates with improved patient survival, and here we demonstrate in an immunocompetent murine model that colon tumors expressing LIGHT stimulate lymphocyte proliferation and tumor cell-specific antitumor immune responses. In this model, increasing LIGHT expression in the microenvironment of either primary tumors or liver metastases triggered regression of established tumors and slowed the growth of liver metastases, driven by cytotoxic T-lymphocyte-mediated antitumor immunity. These responses corresponded with significant increases in tumor-infiltrating lymphocytes and increased expression of lymphocyte-homing signals in the metastatic tumors. Furthermore, we demonstrated evidence of durable tumor-specific antitumor immunity. In conclusion, increasing LIGHT expression increased T-cell proliferation, activation, and infiltration, resulting in enhanced tumor-specific immune-mediated tumor regressions in primary tumors and colorectal liver metastases. Mechanisms to increase LIGHT in the colon cancer microenvironment warrant further investigation and hold promise as an immunotherapeutic strategy. Cancer Res; 77(8); 1880-91. ©2017 AACR.
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Affiliation(s)
- Guilin Qiao
- Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, Illinois
| | - Jianzhong Qin
- Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, Illinois
| | - Nicholas Kunda
- Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, Illinois
| | - Jed F Calata
- Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, Illinois
| | - Dolores L Mahmud
- Department of Hematology and Oncology, University of Illinois at Chicago, Chicago, Illinois
| | - Peter Gann
- Department of Pathology, University of Illinois at Chicago, Chicago, Illinois
| | - Yang-Xin Fu
- Department of Pathology, University of Texas Southwestern, Dallas, Texas
| | - Steven A Rosenberg
- Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Bellur S Prabhakar
- Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois
| | - Ajay V Maker
- Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, Illinois.
- Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois
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Teraoku H, Morine Y, Ikemoto T, Saito Y, Yamada S, Yoshikawa M, Takasu C, Higashijima J, Imura S, Shimada M. Role of thrombospondin-1 expression in colorectal liver metastasis and its molecular mechanism. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2016; 23:565-73. [PMID: 27404020 DOI: 10.1002/jhbp.376] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/04/2016] [Accepted: 07/08/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND Thrombospondin-1 (THBS-1), a glycoprotein, is an endogenous inhibitor of angiogenesis and tumor growth. In this study, we investigated the clinical role and mechanism of THBS-1 expression in colorectal liver metastases, focusing on the relationships between its expression and tumor growth, epithelial-mesenchymal transition (EMT), and expression of other relevant molecules. METHODS Ninety-four patients who initially underwent curative hepatic resection were enrolled in this study and correlations between expression of THBS-1 (THBS-1 high [n = 35] and THBS-1 low [n = 59]) and tumor growth, Ki-67 labeling index (Ki-67 LI), expression of other relevant molecules, and microvessel density (MVD) investigated. RESULTS THBS-1 low expression correlated with more advanced grade of liver and lymph node metastases and significantly worse overall survival than strong THBS-1 expression (3-year survival: 96.7% vs. 65.4%, P < 0.01). Multivariate analysis identified THBS-1 low expression as an independent prognostic factor (HR 2.82, 95% CI 1.21-7.71, P = 0.01). THBS-1 low expression correlated positively with high Ki-67 LI (P < 0.05) and inversely with E-cadherin (P < 0.05) and hypoxia inducible factor-1α (HIF-1α) expression (P < 0.05); THBS-1 expression and MVD were not significantly correlated. CONCLUSIONS Low THBS-1 expression may be an independent poor prognostic factor that affects tumor growth and EMT acquisition. Additionally, THBS-1 may be regulated by the HIF-1 pathway.
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Affiliation(s)
- Hiroki Teraoku
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Yuji Morine
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Tetsuya Ikemoto
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Yu Saito
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Shinichiro Yamada
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Masato Yoshikawa
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Chie Takasu
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Jun Higashijima
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Satoru Imura
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Mitsuo Shimada
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
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Karagkounis G, Akyuz M, Guerron AD, Yazici P, Aucejo FN, Quintini C, Miller CM, Vogt DP, Fung JJ, Berber E. Perioperative and oncologic outcomes of minimally invasive liver resection for colorectal metastases: A case-control study of 130 patients. Surgery 2016; 160:1097-1103. [PMID: 27486002 DOI: 10.1016/j.surg.2016.04.043] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Revised: 04/14/2016] [Accepted: 04/16/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Our aim was to compare the perioperative and oncologic outcomes of open liver resection and minimally invasive liver resection in the management of colorectal liver metastases. METHODS Patients who underwent minimally invasive liver resection for colorectal liver metastases between January 2006 and June 2015 at a single center were identified and matched by extent of resection to consecutive open liver resection patients from the same period. Clinicopathologic characteristics, perioperative data, recurrence, and survival outcomes were collected and analyzed based on intention-to-treat. RESULTS Sixty-five patients underwent minimally invasive liver resection during this period and were matched to 65 consecutive open liver resection patients, with similar baseline demographic, tumor, and chemotherapy parameters. Conversion to open occurred in 5 (7.7%) minimally invasive liver resection patients. R0 resection rates and operative times were comparable, but the estimated blood loss was less in the minimally invasive liver resection group (median 200 mL vs 400 mL, P < .001), as were perioperative transfusion rates (4.6% vs 15.4%, P = .04). The duration of stay was shorter after minimally invasive liver resection (median 4 days vs 6 days, P < .001), while major and minor complication rates were similar and no perioperative mortality was recorded. At a median follow-up of 28 months, there was no difference regarding disease-free (P = .90) or overall survival (P = .37). CONCLUSION In selected patients with colorectal liver metastases, minimally invasive liver resection resulted in similar oncologic outcomes, with decreased blood loss and shorter duration of stay compared to patients who underwent open liver resection.
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Affiliation(s)
| | - Muhammet Akyuz
- Department of General Surgery, Cleveland Clinic, Cleveland, OH
| | | | - Pinar Yazici
- Department of General Surgery, Cleveland Clinic, Cleveland, OH
| | | | | | | | - David P Vogt
- Department of General Surgery, Cleveland Clinic, Cleveland, OH
| | - John J Fung
- Department of General Surgery, Cleveland Clinic, Cleveland, OH
| | - Eren Berber
- Department of General Surgery, Cleveland Clinic, Cleveland, OH.
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Two cases of laparoscopic simultaneous resection of colorectal cancer and synchronous liver metastases in elderly patients. Int J Surg Case Rep 2016; 26:134-7. [PMID: 27490681 PMCID: PMC4972898 DOI: 10.1016/j.ijscr.2016.07.030] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2016] [Revised: 07/23/2016] [Accepted: 07/23/2016] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION The laparoscopic resection of colorectal cancer and laparoscopic liver surgery are widely considered to be safe. Recently, it has been reported that the simultaneous laparoscopic resection of primary colorectal cancer and liver metastasis is technically feasible and safe when it is performed at experienced centers. However, the feasibility of simultaneous laparoscopic procedures for colorectal cancer and synchronous colorectal liver metastases in elderly patients has not been studied sufficiently. In this study, two cases in which elderly patients with colorectal cancer and synchronous liver metastases were treated with simultaneous laparoscopic resection are reported. PRESENTATION OF CASES An 83-year-old female was diagnosed with ascending colon cancer and synchronous hepatic metastases. Simultaneous laparoscopic resection of the primary colon cancer and the liver metastasis was performed. Another tiny hepatic metastasis was subsequently detected in the right hepatic lobe. It was treated with hand-assisted radiofrequency ablation (RFA). The total operative time was 470min, and 340g of intraoperative blood loss occurred. The other case involved a 78-year-old male who was diagnosed with ascending colon cancer and synchronous hepatic metastasis in the right hepatic lobe. Simultaneous laparoscopic resection of the primary colon tumor and liver metastasis was performed. The total operative time was 471min, and 240g of intraoperative blood loss occurred. The postoperative courses of both patients were uneventful. DISCUSSION AND CONCLUSION Our results indicate that simultaneous laparoscopic resection of colorectal cancer and synchronous liver metastases is feasible and safe in elderly patients.
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Shady W, Kishore S, Gavane S, Do RK, Osborne JR, Ulaner GA, Gonen M, Ziv E, Boas FE, Sofocleous CT. Metabolic tumor volume and total lesion glycolysis on FDG-PET/CT can predict overall survival after (90)Y radioembolization of colorectal liver metastases: A comparison with SUVmax, SUVpeak, and RECIST 1.0. Eur J Radiol 2016; 85:1224-31. [PMID: 27161074 DOI: 10.1016/j.ejrad.2016.03.029] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 03/23/2016] [Accepted: 03/30/2016] [Indexed: 12/12/2022]
Abstract
PURPOSE To compare the performance of 4 metrics of metabolic response on FDG-PET/CT against RECIST 1.0 for determining response and predicting overall survival (OS) following (90)Y resin microspheres radioembolization of colorectal liver metastases (CLM). METHODS We conducted an IRB-waived retrospective review of our radioembolization database to identify patients with unresectable CLM treated between December 2009 and December 2013. We included patients who had both PET/CT and contrast enhanced CT (CECT) available at baseline and on the first follow-up post-radioembolization. On baseline CECT up to five target tumors were chosen per patient according to RECIST 1.0. Four metrics of FDG-avidity (SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG)) on PET/CT were measured for the same target tumors. Using RECIST 1.0, patients were classified as no progression (partial response or stable disease) and progression. For each PET metric, a cut-off point of ≥30% decrease was chosen to define response. OS was calculated from the time of radioembolization using Kaplan-Meier methodology. The log-rank test was used for univariate analysis to identify predictors of OS. RESULTS The study enrolled 49 patients with 119 target tumors; a median of 2 (range: 1-5) tumors were selected per patient. Median OS was 12.7 months (95%CI: 7.2-16.7). Response by MTV (P=0.035) and TLG (P=0.044) reached statistical significance in predicting OS. Response by SUVmax (P=0.21), SUVpeak (P=0.20) or no progression by RECIST 1.0 (P=0.44) did not predict OS. CONCLUSION Metabolic response based on changes in MTV and TLG can predict OS post-radioembolization of CLM.
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Affiliation(s)
- Waleed Shady
- Section of Interventional Radiology, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Sirish Kishore
- Department of Nuclear medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Somali Gavane
- Department of Nuclear medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Richard K Do
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Joseph R Osborne
- Department of Nuclear medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Gary A Ulaner
- Department of Nuclear medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Etay Ziv
- Section of Interventional Radiology, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Franz E Boas
- Section of Interventional Radiology, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Constantinos T Sofocleous
- Section of Interventional Radiology, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States.
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Siva S, Kron T, Bressel M, Haas M, Mai T, Vinod S, Sasso G, Wong W, Le H, Eade T, Hardcastle N, Chesson B, Pham D, Høyer M, Montgomery R, Ball D. A randomised phase II trial of Stereotactic Ablative Fractionated radiotherapy versus Radiosurgery for Oligometastatic Neoplasia to the lung (TROG 13.01 SAFRON II). BMC Cancer 2016; 16:183. [PMID: 26944262 PMCID: PMC4778366 DOI: 10.1186/s12885-016-2227-z] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Accepted: 02/28/2016] [Indexed: 12/15/2022] Open
Abstract
Background Stereotactic ablative body radiotherapy (SABR) is emerging as a non-invasive method for precision irradiation of lung tumours. However, the ideal dose/fractionation schedule is not yet known. The primary purpose of this study is to assess safety and efficacy profile of single and multi-fraction SABR in the context of pulmonary oligometastases. Methods/Design The TROG 13.01/ALTG 13.001 clinical trial is a multicentre unblinded randomised phase II study. Eligible patients have up to three metastases to the lung from any non-haematological malignancy, each < 5 cm in size, non-central targets, and have all primary and extrathoracic disease controlled with local therapies. Patients are randomised 1:1 to a single fraction of 28Gy versus 48Gy in four fractions of SABR. The primary objective is to assess the safety of each treatment arm, with secondary objectives including assessment of quality of life, local efficacy, resource use and costs, overall and disease free survival and time to distant failure. Outcomes will be stratified by number of metastases and origin of the primary disease (colorectal versus non-colorectal primary). Planned substudies include an assessment of the impact of online e-Learning platforms for lung SABR and assessment of the effect of SABR fractionation on the immune responses. A total of 84 patients are required to complete the study. Discussion Fractionation schedules have not yet been investigated in a randomised fashion in the setting of oligometastatic disease. Assuming the likelihood of similar clinical efficacy in both arms, the present study design allows for exploration of the hypothesis that cost implications of managing potentially increased toxicities from single fraction SABR will be outweighed by costs associated with delivering multiple-fraction SABR. Trials registration ACTRN12613001157763, registered 17th October 2013
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Affiliation(s)
- Shankar Siva
- Peter MacCallum Cancer Centre, 2 St Andrews Place, East Melbourne, 3002, Australia. .,University of Melbourne, Royal Parade, Parkville, 8006, Australia.
| | - Tomas Kron
- Peter MacCallum Cancer Centre, 2 St Andrews Place, East Melbourne, 3002, Australia. .,University of Melbourne, Royal Parade, Parkville, 8006, Australia.
| | - Mathias Bressel
- Peter MacCallum Cancer Centre, 2 St Andrews Place, East Melbourne, 3002, Australia.
| | - Marion Haas
- Centre for Health Economics Research and Evaluation, University of Technology Sydney, PO Box 123, Broadway Sydney, 2007, Australia.
| | - Tao Mai
- Princess Alexandra Hospital, Ipswich Rd, Woolloongabba, Qld, 4102, Australia.
| | - Shalini Vinod
- Cancer Therapy Centre, Liverpool Hospital, Locked Bag 7103, Liverpool BC, NSW, 1871, Australia.
| | - Giuseppe Sasso
- Radiation Oncology Department, Auckland City Hospital, Auckland, New Zealand.
| | - Wenchang Wong
- Department of Radiation Oncology, Prince of Wales Hospital, Barker St, Randwick, NSW, 2031, Australia.
| | - Hien Le
- Department of Radiation Oncology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia.
| | - Thomas Eade
- Department of Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, 2065, NSW, Australia.
| | - Nicholas Hardcastle
- Department of Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, 2065, NSW, Australia.
| | - Brent Chesson
- Peter MacCallum Cancer Centre, 2 St Andrews Place, East Melbourne, 3002, Australia.
| | - Daniel Pham
- Peter MacCallum Cancer Centre, 2 St Andrews Place, East Melbourne, 3002, Australia.
| | - Morten Høyer
- Department of Oncology, Aarhus University Hospital, Aarhus, 8000, Denmark.
| | - Rebecca Montgomery
- Trans Tasman Radiation Oncology Group (TROG), PO Box 88, Waratah, 2298, Australia.
| | - David Ball
- Peter MacCallum Cancer Centre, 2 St Andrews Place, East Melbourne, 3002, Australia. .,University of Melbourne, Royal Parade, Parkville, 8006, Australia.
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Vilgrain V, Esvan M, Ronot M, Caumont-Prim A, Aubé C, Chatellier G. A meta-analysis of diffusion-weighted and gadoxetic acid-enhanced MR imaging for the detection of liver metastases. Eur Radiol 2016; 26:4595-4615. [PMID: 26883327 DOI: 10.1007/s00330-016-4250-5] [Citation(s) in RCA: 95] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Revised: 01/22/2016] [Accepted: 01/25/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To obtain the diagnostic performance of diffusion-weighted (DW) and gadoxetic-enhanced magnetic resonance (MR) imaging in the detection of liver metastases. METHODS A comprehensive search (EMBASE, PubMed, Cochrane) was performed to identify relevant articles up to June 2015. Inclusion criteria were: liver metastases, DW-MR imaging and/or gadoxetic acid-enhanced MR imaging, and per-lesion statistics. The reference standard was histopathology, intraoperative observation and/or follow-up. Sources of bias were assessed using the QUADAS-2 tool. A linear mixed-effect regression model was used to obtain sensitivity estimates. RESULTS Thirty-nine articles were included (1,989 patients, 3,854 metastases). Sensitivity estimates for DW-MR imaging, gadoxetic acid-enhanced MR imaging and the combined sequence for detecting liver metastases on a per-lesion basis was 87.1 %, 90.6 % and 95.5 %, respectively. Sensitivity estimates by gadoxetic acid-enhanced MR imaging and the combined sequence were significantly better than DW-MR imaging (p = 0.0001 and p < 0.0001, respectively), and the combined MR sequence was significantly more sensitive than gadoxetic acid-enhanced MR imaging (p < 0.0001). Similar results were observed in articles that compared the three techniques simultaneously, with only colorectal liver metastases and in liver metastases smaller than 1 cm. CONCLUSIONS In patients with liver metastases, combined DW-MR and gadoxetic acid-enhanced MR imaging has the highest sensitivity for detecting liver metastases on a per-lesion basis. KEY POINTS • DW-MRI is less sensitive than gadoxetic acid-enhanced MRI for detecting liver metastases • DW-MRI and gadoxetic acid-enhanced MRI is the best combination • Same results are observed in colorectal liver metastases • Same results are observed in liver metastases smaller than 1 cm • Same results are observed when histopathology alone is the reference standard.
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Affiliation(s)
- Valérie Vilgrain
- Department of Radiology, Assistance Publique-Hôpitaux de Paris, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France. .,University Paris Diderot, Sorbonne Paris Cité, Paris, France. .,INSERM U1149, Centre de Recherche Biomédicale Bichat-Beaujon, CRB3, Paris, France.
| | - Maxime Esvan
- Hôpital européen Georges-Pompidou, Unité d'Épidémiologie et de Recherche Clinique, 75015, Paris, France.,INSERM, Centre d'Investigation Clinique 1418, module Épidémiologie Clinique, 75015, Paris, France
| | - Maxime Ronot
- Department of Radiology, Assistance Publique-Hôpitaux de Paris, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France.,University Paris Diderot, Sorbonne Paris Cité, Paris, France.,INSERM U1149, Centre de Recherche Biomédicale Bichat-Beaujon, CRB3, Paris, France
| | - Aurore Caumont-Prim
- Hôpital européen Georges-Pompidou, Unité d'Épidémiologie et de Recherche Clinique, 75015, Paris, France.,INSERM, Centre d'Investigation Clinique 1418, module Épidémiologie Clinique, 75015, Paris, France
| | - Christophe Aubé
- Department of Radiology, CHU d'Angers, Angers, France.,Laboratoire HIFIH, LUNAM, Université d'Angers, Angers, France
| | - Gilles Chatellier
- Hôpital européen Georges-Pompidou, Unité d'Épidémiologie et de Recherche Clinique, 75015, Paris, France.,INSERM, Centre d'Investigation Clinique 1418, module Épidémiologie Clinique, 75015, Paris, France.,Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, 75006, Paris, France
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